{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:27:48Z","timestamp":1790699268491,"version":"4.1.0"},"reference-count":244,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:00:00Z","timestamp":1622592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY028153"],"award-info":[{"award-number":["R01EY028153"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY019007"],"award-info":[{"award-number":["P30EY019007"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Departmental Grant"],"award-info":[{"award-number":["Departmental Grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glaucoma is a chronic neurodegenerative disease characterized by apoptosis of retinal ganglion cell (RGC) somas, degeneration of axons, and loss of synapses at dendrites and axon terminals. Glaucomatous neurodegeneration encompasses multiple triggers, multiple cell types, and multiple molecular pathways through the etiological paths with biomechanical, vascular, metabolic, oxidative, and inflammatory components. As much as intrinsic responses of RGCs themselves, divergent responses and intricate interactions of the surrounding glia also play decisive roles for the cell fate. Seen from a broad perspective, multitarget treatment strategies have a compelling pathophysiological basis to more efficiently manipulate multiple pathogenic processes at multiple injury sites in such a multifactorial neurodegenerative disease. Despite distinct molecular programs for somatic and axonal degeneration, mitochondrial dysfunction and glia-driven neuroinflammation present interdependent processes with widespread impacts in the glaucomatous retina and optic nerve. Since dysfunctional mitochondria stimulate inflammatory responses and proinflammatory mediators impair mitochondria, mitochondrial restoration may be immunomodulatory, while anti-inflammatory treatments protect mitochondria. Manipulation of these converging routes may thus allow a unified treatment strategy to protect RGC axons, somas, and synapses. This review presents an overview of recent research advancements with emphasis on potential treatment targets to achieve the best treatment efficacy to preserve visual function in glaucoma.<\/jats:p>","DOI":"10.3390\/cells10061372","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T10:38:39Z","timestamp":1622630319000},"page":"1372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Multifactorial Pathogenic Processes of Retinal Ganglion Cell Degeneration in Glaucoma towards Multi-Target Strategies for Broader Treatment Effects"],"prefix":"10.3390","volume":"10","author":[{"given":"G\u00fclg\u00fcn","family":"Tezel","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University, Edward S. Harkness Eye Institute, 635 W 165th St., Box 102, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100769","DOI":"10.1016\/j.preteyeres.2019.07.002","article-title":"Axon injury signaling and compartmentalized injury response in glaucoma","volume":"73","author":"Libby","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/bs.pbr.2020.05.027","article-title":"A broad perspective on the molecular regulation of retinal ganglion cell degeneration in glaucoma","volume":"256","author":"Tezel","year":"2020","journal-title":"Prog. Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1146\/annurev.genom.6.080604.162209","article-title":"Complex genetics of glaucoma susceptibility","volume":"6","author":"Libby","year":"2005","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1093\/hmg\/ddx184","article-title":"Genetics of glaucoma","volume":"26","author":"Wiggs","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.preteyeres.2005.04.004","article-title":"Glaucoma: Thinking in new ways-a role for autonomous axonal self-destruction and other compartmentalised processes?","volume":"24","author":"Whitmore","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1083\/jcb.200706181","article-title":"Axons of retinal ganglion cells are insulted in the optic nerve early in DBA\/2J glaucoma","volume":"179","author":"Howell","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1523\/JNEUROSCI.4443-07.2008","article-title":"Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of glaucoma","volume":"28","author":"Buckingham","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Libby, R.T., Li, Y., Savinova, O.V., Barter, J., Smith, R.S., Nickells, R.W., and John, S.W. (2005). Susceptibility to neurodegeneration in a glaucoma is modified by bax gene dosage. PLoS Genet., 1.","DOI":"10.1371\/journal.pgen.0010004"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1111\/j.1460-9568.2008.06426.x","article-title":"The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model","volume":"28","author":"Beirowski","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1523\/JNEUROSCI.0359-11.2011","article-title":"The polymodal ion channel transient receptor potential vanilloid 4 modulates calcium flux, spiking rate, and apoptosis of mouse retinal ganglion cells","volume":"31","author":"Ryskamp","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1113\/jphysiol.2012.227983","article-title":"Neurons respond directly to mechanical deformation with pannexin-mediated ATP release and autostimulation of P2X7 receptors","volume":"590","author":"Xia","year":"2012","journal-title":"J. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1080\/19336950.2015.1009272","article-title":"Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress","volume":"9","author":"Sappington","year":"2015","journal-title":"Channels"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.1038\/s41598-018-23894-2","article-title":"Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells","volume":"8","author":"Dvoriantchikova","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","first-page":"192","article-title":"Changes in Thy1 gene expression associated with damaged retinal ganglion cells","volume":"7","author":"Schlamp","year":"2001","journal-title":"Mol. Vis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/02713680500545671","article-title":"Downregulation of Thy1 in retinal ganglion cells in experimental glaucoma","volume":"31","author":"Huang","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1523\/JNEUROSCI.3714-07.2008","article-title":"Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model","volume":"28","author":"Soto","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1167\/iovs.11-8872","article-title":"Silencing of Fem1cR3 gene expression in the DBA\/2J mouse precedes retinal ganglion cell death and is associated with histone deacetylase activity","volume":"53","author":"Pelzel","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Williams, P.A., Howell, G.R., Barbay, J.M., Braine, C.E., Sousa, G.L., John, S.W., and Morgan, J.E. (2013). Retinal ganglion cell dendritic atrophy in DBA\/2J glaucoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072282"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17444","DOI":"10.1523\/JNEUROSCI.5461-12.2013","article-title":"Differential progression of structural and functional alterations in distinct retinal ganglion cell types in a mouse model of glaucoma","volume":"33","author":"Inman","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1073\/pnas.1419921112","article-title":"Elevated intraocular pressure decreases response sensitivity of inner retinal neurons in experimental glaucoma mice","volume":"112","author":"Pang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E3839","DOI":"10.1073\/pnas.1608769114","article-title":"Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective","volume":"114","author":"Harder","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Berry, R.H., Qu, J., John, S.W., Howell, G.R., and Jakobs, T.C. (2015). Synapse loss and dendrite remodeling in a mouse model of glaucoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144341"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1523\/JNEUROSCI.1419-14.2015","article-title":"Characteristic patterns of dendritic remodeling in early-stage glaucoma: Evidence from genetically identified retinal ganglion cell types","volume":"35","author":"Huberman","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"fcz035","DOI":"10.1093\/braincomms\/fcz035","article-title":"Midget retinal ganglion cell dendritic and mitochondrial degeneration is an early feature of human glaucoma","volume":"1","author":"Tribble","year":"2019","journal-title":"Brain Commun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Aydin, R., Baris, M., Durmaz-Engin, C., Al-Aswad, L.A., Blumberg, D.M., Cioffi, G.A., Liebmann, J.M., Tezel, T.H., and Tezel, G. (2021). Early localized alterations of the retinal inner plexiform layer in association with visual field worsening in glaucoma patients. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247401"},{"key":"ref_28","first-page":"2696","article-title":"Immunohistochemical changes in rat retinas at various time periods of elevated intraocular pressure","volume":"15","author":"Hernandez","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/cne.24074","article-title":"Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas","volume":"527","author":"Akopian","year":"2019","journal-title":"J. Comp. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1136\/bjo.2005.086769","article-title":"Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex","volume":"90","author":"Gupta","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.visres.2010.08.003","article-title":"Dendrite plasticity in the lateral geniculate nucleus in primate glaucoma","volume":"51","author":"Ly","year":"2011","journal-title":"Vis. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1167\/iovs.14-13902","article-title":"An investigation of lateral geniculate nucleus volume in patients with primary open-angle glaucoma using 7 tesla magnetic resonance imaging","volume":"55","author":"Lee","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schlamp, C.L., Li, Y., Dietz, J.A., Janssen, K.T., and Nickells, R.W. (2006). Progressive ganglion cell loss and optic nerve degeneration in DBA\/2J mice is variable and asymmetric. BMC Neurosci., 7.","DOI":"10.1186\/1471-2202-7-66"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1073\/pnas.0913141107","article-title":"Distal axonopathy with structural persistence in glaucomatous neurodegeneration","volume":"107","author":"Crish","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.coph.2012.09.013","article-title":"Immune regulation toward immunomodulation for neuroprotection in glaucoma","volume":"13","author":"Tezel","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/bs.pmbts.2015.06.010","article-title":"Neuroinflammation in glaucoma and optic nerve damage","volume":"134","author":"Nickells","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.exer.2017.02.014","article-title":"Lasker\/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration Participants. Neuroinflammation in glaucoma: A new opportunity","volume":"157","author":"Williams","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1007\/s40135-019-00212-1","article-title":"Immunomodulation as a neuroprotective strategy for glaucoma treatment","volume":"7","author":"Baris","year":"2019","journal-title":"Curr. Ophthalmol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1038\/s41598-019-39141-1","article-title":"Transcriptomic profiles of retinal ganglion cells are defined by the magnitude of intraocular pressure elevation in adult mice","volume":"9","author":"Park","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13041-020-00603-7","article-title":"Ocular hypertension suppresses homeostatic gene expression in optic nerve head microglia of DBA\/2 J mice","volume":"13","author":"Tribble","year":"2020","journal-title":"Mol. Brain."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/prca.201300115","article-title":"A decade of proteomics studies of glaucomatous neurodegeneration","volume":"8","author":"Tezel","year":"2014","journal-title":"Proteom. Clin. Appl."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1167\/iovs.18-24938","article-title":"A metabolomics profiling of glaucoma points to mitochondrial dysfunction, senescence, and polyamines deficiency","volume":"59","author":"Leruez","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1167\/iovs.18-25802","article-title":"Optic nerve lipidomics reveal impaired glucosylsphingosine lipids pathway in glaucoma","volume":"60","author":"Chauhan","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.semcdb.2019.05.028","article-title":"Mitochondria at the interface between neurodegeneration and neuroinflammation","volume":"99","author":"Bader","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"132931","DOI":"10.1016\/j.neulet.2017.06.050","article-title":"Inflammation and mitochondrial dysfunction: A vicious circle in neurodegenerative disorders?","volume":"710","author":"Witte","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1523\/JNEUROSCI.5956-09.2010","article-title":"Metabolic vulnerability disposes retinal ganglion cell axons to dysfunction in a model of glaucomatous degeneration","volume":"30","author":"Baltan","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1523\/JNEUROSCI.4065-10.2011","article-title":"Axonal degeneration is mediated by the mitochondrial permeability transition pore","volume":"31","author":"Barrientos","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"478","DOI":"10.3389\/fnins.2017.00478","article-title":"Investigations into hypoxia and oxidative stress at the optic nerve head in a rat model of glaucoma","volume":"11","author":"Chidlow","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_49","first-page":"764","article-title":"Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma","volume":"41","author":"Pease","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.exer.2009.02.004","article-title":"Neurotrophin roles in retinal ganglion cell survival: Lessons from rat glaucoma models","volume":"88","author":"Johnson","year":"2009","journal-title":"Exp. Eye Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1083\/jcb.201108111","article-title":"Axon degeneration: Molecular mechanisms of a self-destruction pathway","volume":"196","author":"Wang","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2017.01.002","article-title":"BAX to basics: How the BCL2 gene family controls the death of retinal ganglion cells","volume":"57","author":"Maes","year":"2017","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1167\/iovs.08-3013","article-title":"Effect of CNTF on retinal ganglion cell survival in experimental glaucoma","volume":"50","author":"Pease","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13469","DOI":"10.1073\/pnas.0906678106","article-title":"Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma","volume":"106","author":"Lambiase","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/IJG.0b013e3181d787e5","article-title":"Ocular application of nerve growth factor protects degenerating retinal ganglion cells in a rat model of glaucoma","volume":"20","author":"Colafrancesco","year":"2011","journal-title":"J. Glaucoma"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s40259-013-0079-5","article-title":"Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial","volume":"28","author":"Ferrari","year":"2014","journal-title":"BioDrugs"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mito.2016.11.009","article-title":"Visual light effects on mitochondria: The potential implications in relation to glaucoma","volume":"36","author":"Osborne","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_58","first-page":"100881","article-title":"Retinal energy metabolism in health and glaucoma","volume":"10","author":"Casson","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10515","DOI":"10.1073\/pnas.1509879112","article-title":"In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS","volume":"112","author":"Takihara","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","first-page":"1331","article-title":"Increased optic atrophy type 1 expression protects retinal ganglion cells in a mouse model of glaucoma","volume":"16","author":"Ju","year":"2010","journal-title":"Mol. Vis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e1839","DOI":"10.1038\/cddis.2015.180","article-title":"DRP1 inhibition rescues retinal ganglion cells and their axons by preserving mitochondrial integrity in a mouse model of glaucoma","volume":"6","author":"Kim","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1167\/iovs.14-16126","article-title":"Mitochondrial morphology differences and mitophagy deficit in murine glaucomatous optic nerve","volume":"56","author":"Coughlin","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1016\/j.survophthal.2007.08.012","article-title":"What is the present pathogenetic concept of glaucomatous optic neuropathy?","volume":"52","author":"Flammer","year":"2007","journal-title":"Surv. Ophthalmol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.exer.2010.09.002","article-title":"The complex interaction between ocular perfusion pressure and ocular blood flow-relevance for glaucoma","volume":"93","author":"Schmidl","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"452","DOI":"10.3389\/fcell.2020.00452","article-title":"The neurovascular unit in glaucomatous neurodegeneration","volume":"8","author":"Wareham","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/jnr.20573","article-title":"Transfer of glycogen-derived lactate from astrocytes to axons via specific monocarboxylate transporters supports mouse optic nerve activity","volume":"81","author":"Tekkok","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Carreras, F.J., Aranda, C.J., Porcel, D., Rodriguez-Hurtado, F., Martinez-Agustin, O., and Zarzuelo, A. (2015). Expression of glucose transporters in the prelaminar region of the optic-nerve head of the pig as determined by immunolabeling and tissue culture. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128516"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.neuron.2016.05.016","article-title":"Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism","volume":"91","author":"Saab","year":"2016","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1016\/j.jmb.2019.03.005","article-title":"Lactate-mediated protection of retinal ganglion cells","volume":"431","author":"Vohra","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1167\/iovs.18-25536","article-title":"Distribution and activity of mitochondrial proteins in vascular and avascular retinas: Implications for retinal metabolism","volume":"60","author":"Chidlow","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5122","DOI":"10.1523\/JNEUROSCI.3652-17.2018","article-title":"Structural and functional rescue of chronic metabolically stressed optic nerves through respiration","volume":"38","author":"Pappenhagen","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"104944","DOI":"10.1016\/j.nbd.2020.104944","article-title":"MCT2 overexpression rescues metabolic vulnerability and protects retinal ganglion cells in two models of glaucoma","volume":"141","author":"Pappenhagen","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1001\/archophthalmol.2011.269","article-title":"Protection of retinal ganglion cells and the optic nerve during short-term hyperglycemia in experimental glaucoma","volume":"129","author":"Ebneter","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ceo.12581","article-title":"Effect of subconjunctival glucose on retinal ganglion cell survival in experimental retinal ischaemia and contrast sensitivity in human glaucoma","volume":"44","author":"Shibeeb","year":"2016","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1016\/j.ophtha.2013.12.011","article-title":"Glucose-induced temporary visual recovery in primary open-angle glaucoma: A double-blind, randomized study","volume":"121","author":"Casson","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1126\/science.1058079","article-title":"Cooperation and competition in the evolution of ATP-producing pathways","volume":"292","author":"Pfeiffer","year":"2001","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1167\/iovs.15-17294","article-title":"Proteomics analysis of molecular risk factors in the ocular hypertensive human retina","volume":"56","author":"Yang","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1001\/archopht.122.9.1348","article-title":"Hypoxia-inducible factor 1alpha in the glaucomatous retina and optic nerve head","volume":"122","author":"Tezel","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1126\/science.aal0092","article-title":"Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice","volume":"355","author":"Williams","year":"2017","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1167\/iovs.18-24977","article-title":"Evidence of hypoxic glial cells in a model of ocular hypertension","volume":"60","author":"Jassim","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7097","DOI":"10.1007\/s12035-019-1576-4","article-title":"Higher reliance on glycolysis limits glycolytic responsiveness in degenerating glaucomatous optic nerve","volume":"56","author":"Jassim","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.preteyeres.2006.07.003","article-title":"Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences","volume":"25","author":"Tezel","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"33619","DOI":"10.1073\/pnas.2014213117","article-title":"Disturbed glucose and pyruvate metabolism in glaucoma with neuroprotection by pyruvate or rapamycin","volume":"117","author":"Harder","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.coph.2012.09.008","article-title":"Oxidative stress and mitochondrial dysfunction in glaucoma","volume":"13","author":"Chrysostomou","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1093\/brain\/awq105","article-title":"Superoxide is an associated signal for apoptosis in axonal injury","volume":"133","author":"Kanamori","year":"2010","journal-title":"Brain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.1167\/iovs.04-0490","article-title":"Caspase-independent component of retinal ganglion cell death, in vitro","volume":"45","author":"Tezel","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1167\/iovs.05-0208","article-title":"Proteomic identification of oxidatively modified retinal proteins in a chronic pressure-induced rat model of glaucoma","volume":"46","author":"Tezel","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1167\/iovs.06-0810","article-title":"Mechanisms of immune system activation in glaucoma: Oxidative stress-stimulated antigen presentation by the retina and optic nerve head glia","volume":"48","author":"Tezel","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.exer.2010.07.009","article-title":"The immune response in glaucoma: A perspective on the roles of oxidative stress","volume":"93","author":"Tezel","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Inman, D.M., Lambert, W.S., Calkins, D.J., and Horner, P.J. (2013). alpha-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065389"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1167\/iovs.16-19153","article-title":"Antioxidant treatment limits neuroinflammation in experimental glaucoma","volume":"57","author":"Yang","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1167\/iovs.10-5407","article-title":"Glaucomatous tissue stress and the regulation of immune response through glial toll-like receptor signaling","volume":"51","author":"Luo","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1167\/iovs.13-12564","article-title":"Coenzyme Q10 inhibits glutamate excitotoxicity and oxidative stress-mediated mitochondrial alteration in a mouse model of glaucoma","volume":"55","author":"Lee","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.mito.2017.05.010","article-title":"Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension","volume":"36","author":"Davis","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Garcia-Medina, J.J., Rubio-Velazquez, E., Lopez-Bernal, M.D., Cobo-Martinez, A., Zanon-Moreno, V., Pinazo-Duran, M.D., and Del-Rio-Vellosillo, M. (2020). Glaucoma and antioxidants: Review and update. Antioxidants, 9.","DOI":"10.3390\/antiox9111031"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Tribble, J.R., Hui, F., Joe, M., Bell, K., Chrysostomou, V., Crowston, J.G., and Williams, P.A. (2021). Targeting diet and exercise for neuroprotection and neurorecovery in glaucoma. Cells, 10.","DOI":"10.3390\/cells10020295"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aac4854","article-title":"NAD(+) in aging, metabolism, and neurodegeneration","volume":"350","author":"Verdin","year":"2015","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.cmet.2019.09.001","article-title":"NAD(+) in brain aging and neurodegenerative disorders","volume":"30","author":"Lautrup","year":"2019","journal-title":"Cell Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1167\/iovs.12-10861","article-title":"Protection of mouse retinal ganglion cell axons and soma from glaucomatous and ischemic injury by cytoplasmic overexpression of Nmnat1","volume":"54","author":"Zhu","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"6526","DOI":"10.1523\/JNEUROSCI.1429-09.2009","article-title":"Transgenic mice expressing the Nmnat1 protein manifest robust delay in axonal degeneration in vivo","volume":"29","author":"Sasaki","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3389\/fnins.2017.00232","article-title":"Nicotinamide and WLD(S) act together to prevent neurodegeneration in glaucoma","volume":"11","author":"Williams","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.nbd.2013.07.007","article-title":"Maintaining energy homeostasis is an essential component of Wld(S)-mediated axon protection","volume":"59","author":"Shen","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e201912047","DOI":"10.1083\/jcb.201912047","article-title":"SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration","volume":"219","author":"Ko","year":"2020","journal-title":"J. Cell Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/ceo.13818","article-title":"Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial","volume":"48","author":"Hui","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/19491034.2016.1264552","article-title":"Sirtuins and DNA damage repair: SIRT7 comes to play","volume":"8","author":"Vazquez","year":"2017","journal-title":"Nucleus"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/iovs.61.3.13","article-title":"Protection of the retinal ganglion cells: Intravitreal injection of resveratrol in mouse model of ocular hypertension","volume":"61","author":"Cao","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1167\/iovs.09-3816","article-title":"Altered calcium signaling in an experimental model of glaucoma","volume":"51","author":"Niittykoski","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.nbd.2013.03.009","article-title":"Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration","volume":"56","author":"Ma","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"8442","DOI":"10.1167\/iovs.11-8152","article-title":"Neurodegenerative and inflammatory pathway components linked to TNF-alpha\/TNFR1 signaling in the glaucomatous human retina","volume":"52","author":"Yang","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3049","DOI":"10.1167\/iovs.09-4364","article-title":"Calpain activation in experimental glaucoma","volume":"51","author":"Huang","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Deng, S., Wang, M., Yan, Z., Tian, Z., Chen, H., Yang, X., and Zhuo, Y. (2013). Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077100"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1083\/jcb.201606020","article-title":"GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration","volume":"216","author":"Wakatsuki","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"13321","DOI":"10.1038\/s41598-018-30165-7","article-title":"Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas","volume":"8","author":"Park","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41420-018-0077-y","article-title":"Contribution of autophagy to ocular hypertension and neurodegeneration in the DBA\/2J spontaneous glaucoma mouse model","volume":"4","author":"Hirt","year":"2018","journal-title":"Cell Death Discov."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8215","DOI":"10.1167\/iovs.15-17885","article-title":"Decreased energy capacity and increased autophagic activity in optic nerve axons with defective anterograde transport","volume":"56","author":"Kleesattel","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41419-017-0146-9","article-title":"Overexpression of parkin protects retinal ganglion cells in experimental glaucoma","volume":"9","author":"Dai","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_117","first-page":"3582","article-title":"Mitochondrial uncoupling protein 2 knock-out promotes mitophagy to decrease retinal ganglion cell death in a mouse model of glaucoma","volume":"39","author":"Hass","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrm.2017.110","article-title":"The mitochondrial UPR: Mechanisms, physiological functions and implications in ageing","volume":"19","author":"Shpilka","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.brainres.2009.10.025","article-title":"Retinal ganglion cell death induced by endoplasmic reticulum stress in a chronic glaucoma model","volume":"1308","author":"Doh","year":"2010","journal-title":"Brain Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1167\/iovs.11-8837","article-title":"Topical ocular sodium 4-phenylbutyrate rescues glaucoma in a myocilin mouse model of primary open-angle glaucoma","volume":"53","author":"Zode","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"5891","DOI":"10.1523\/JNEUROSCI.3709-15.2016","article-title":"Rescue of glaucomatous neurodegeneration by differentially modulating neuronal endoplasmic reticulum stress molecules","volume":"36","author":"Yang","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/s41420-019-0220-4","article-title":"DDIT3 (CHOP) contributes to retinal ganglion cell somal loss but not axonal degeneration in DBA\/2J mice","volume":"5","author":"Marola","year":"2019","journal-title":"Cell Death Discov."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1007\/s12035-019-01783-7","article-title":"BAX-depleted retinal ganglion cells survive and become quiescent following optic nerve damage","volume":"57","author":"Donahue","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"8693","DOI":"10.1523\/JNEUROSCI.20-23-08693.2000","article-title":"Increased production of tumor necrosis factor-alpha by glial cells exposed to simulated ischemia or elevated hydrostatic pressure induces apoptosis in cocultured retinal ganglion cells","volume":"20","author":"Tezel","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_125","first-page":"1787","article-title":"Tumor necrosis factor-alpha and its receptor-1 in the retina of normal and glaucomatous eyes","volume":"42","author":"Tezel","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12974-019-1576-3","article-title":"A small peptide antagonist of the Fas receptor inhibits neuroinflammation and prevents axon degeneration and retinal ganglion cell death in an inducible mouse model of glaucoma","volume":"16","author":"Krishnan","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0002-9440(10)62042-1","article-title":"Transcriptional up-regulation and activation of initiating caspases in experimental glaucoma","volume":"167","author":"Huang","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_128","first-page":"1077","article-title":"Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension","volume":"43","author":"McKinnon","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.1167\/iovs.11-9101","article-title":"An astrocyte-specific proteomic approach to inflammatory responses in experimental rat glaucoma","volume":"53","author":"Tezel","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_130","first-page":"2660","article-title":"Inhibition of caspase activity in retinal cell apoptosis induced by various stimuli in vitro","volume":"40","author":"Tezel","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1006\/mthe.2002.0608","article-title":"Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model","volume":"5","author":"McKinnon","year":"2002","journal-title":"Mol. Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1167\/iovs.07-1344","article-title":"Phosphorylation-dependent interaction with 14-3-3 in the regulation of bad trafficking in retinal ganglion cells","volume":"49","author":"Yang","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cell.2014.11.053","article-title":"Pathological axonal death through a MAPK cascade that triggers a local energy deficit","volume":"160","author":"Yang","year":"2015","journal-title":"Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.exer.2018.03.007","article-title":"Role of SARM1 and DR6 in retinal ganglion cell axonal and somal degeneration following axonal injury","volume":"171","author":"Fernandes","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/brain\/awy338","article-title":"Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease","volume":"142","author":"You","year":"2019","journal-title":"Brain"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1038\/nature07767","article-title":"APP binds DR6 to trigger axon pruning and neuron death via distinct caspases","volume":"457","author":"Nikolaev","year":"2009","journal-title":"Nature"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.nbd.2012.02.003","article-title":"JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death","volume":"46","author":"Fernandes","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/s41419-018-0705-8","article-title":"Jnk2 deficiency increases the rate of glaucomatous neurodegeneration in ocular hypertensive DBA\/2J mice","volume":"9","author":"Harder","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exer.2013.04.021","article-title":"JUN regulates early transcriptional responses to axonal injury in retinal ganglion cells","volume":"112","author":"Fernandes","year":"2013","journal-title":"Exp. Eye Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e2945","DOI":"10.1038\/cddis.2017.338","article-title":"JUN is important for ocular hypertension-induced retinal ganglion cell degeneration","volume":"8","author":"Fernandes","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13024-017-0214-8","article-title":"Together JUN and DDIT3 (CHOP) control retinal ganglion cell death after axonal injury","volume":"12","author":"Fernandes","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.nbd.2014.05.015","article-title":"DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury","volume":"69","author":"Fernandes","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.neuron.2017.06.008","article-title":"Enhanced functional genomic screening identifies novel mediators of dual leucine zipper kinase-dependent injury signaling in neurons","volume":"94","author":"Welsbie","year":"2017","journal-title":"Neuron"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/s41419-018-1079-7","article-title":"Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death","volume":"9","author":"Rausch","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"4039","DOI":"10.1073\/pnas.1211074110","article-title":"DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury","volume":"110","author":"Watkins","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1167\/iovs.02-1136","article-title":"Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma","volume":"44","author":"Tezel","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.brainres.2003.10.029","article-title":"Role of tumor necrosis factor receptor-1 in the death of retinal ganglion cells following optic nerve crush injury in mice","volume":"996","author":"Tezel","year":"2004","journal-title":"Brain Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.exer.2005.08.017","article-title":"Expression of phosphorylated c-Jun N-terminal protein kinase (JNK) in experimental glaucoma in rats","volume":"82","author":"Kwong","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1111\/ejn.12710","article-title":"Tumor necrosis factor-alpha mediates activation of NF-kappaB and JNK signaling cascades in retinal ganglion cells and astrocytes in opposite ways","volume":"40","author":"Dvoriantchikova","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"105258","DOI":"10.1016\/j.nbd.2021.105258","article-title":"Regulation of distinct caspase-8 functions in retinal ganglion cells and astroglia in experimental glaucoma","volume":"150","author":"Yang","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41419-020-02990-0","article-title":"Endothelin 1-induced retinal ganglion cell death is largely mediated by JUN activation","volume":"11","author":"Marola","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molcel.2017.08.017","article-title":"NLRP3 phosphorylation is an essential priming event for inflammasome activation","volume":"68","author":"Song","year":"2017","journal-title":"Mol. Cell."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0079-6123(08)01125-4","article-title":"Astrocytes in glaucomatous optic neuropathy","volume":"173","author":"Hernandez","year":"2008","journal-title":"Prog. Brain Res."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Qu, J., and Jakobs, T.C. (2013). The time course of gene expression during reactive gliosis in the optic nerve. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067094"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1167\/iovs.12-10109","article-title":"Morphology of astrocytes in a glaucomatous optic nerve","volume":"54","author":"Sun","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Tehrani, S., Davis, L., Cepurna, W.O., Choe, T.E., Lozano, D.C., Monfared, A., Cooper, L., Cheng, J., Johnson, E.C., and Morrison, J.C. (2016). Astrocyte structural and molecular response to elevated intraocular pressure occurs rapidly and precedes axonal tubulin rearrangement within the optic nerve head in a rat model. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167364"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Quillen, S., Schaub, J., Quigley, H., Pease, M., Korneva, A., and Kimball, E. (2020). Astrocyte responses to experimental glaucoma in mouse optic nerve head. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238104"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1001\/archopht.117.8.1050","article-title":"Microglia in the optic nerve head and the region of parapapillary chorioretinal atrophy in glaucoma","volume":"117","author":"Neufeld","year":"1999","journal-title":"Arch. Ophthalmol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"6448","DOI":"10.1167\/iovs.10-5284","article-title":"Microglial activation in the visual pathway in experimental glaucoma: Spatiotemporal characterization and correlation with axonal injury","volume":"51","author":"Ebneter","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1002\/cne.22516","article-title":"Early microglia activation in a mouse model of chronic glaucoma","volume":"519","author":"Bosco","year":"2011","journal-title":"J. Comp. Neurol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.exer.2011.01.012","article-title":"Involvement of the CD200 receptor complex in microglia activation in experimental glaucoma","volume":"92","author":"Taylor","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI44646","article-title":"Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma","volume":"121","author":"Howell","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00441-013-1666-y","article-title":"The role of Muller glia and microglia in glaucoma","volume":"353","author":"Seitz","year":"2013","journal-title":"Cell Tissue Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1167\/iovs.17-22531","article-title":"Activation of the NFAT-calcium signaling pathway in human lamina cribrosa cells in glaucoma","volume":"59","author":"Irnaten","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/glia.20962","article-title":"Glaucomatous optic nerve injury involves early astrocyte reactivity and late oligodendrocyte loss","volume":"58","author":"Son","year":"2010","journal-title":"Glia"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1007\/s12035-020-01910-9","article-title":"Sub-region-specific optic nerve head glial activation in glaucoma","volume":"57","author":"Oikawa","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.nbd.2014.07.016","article-title":"Combinatorial targeting of early pathways profoundly inhibits neurodegeneration in a mouse model of glaucoma","volume":"71","author":"Howell","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13024-016-0091-6","article-title":"Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma","volume":"11","author":"Williams","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1016\/j.ymthe.2018.08.017","article-title":"Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma","volume":"26","author":"Bosco","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1186\/s12974-020-02011-z","article-title":"Complement peptide C3a receptor 1 promotes optic nerve degeneration in DBA\/2J mice","volume":"17","author":"Harder","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1172\/JCI61135","article-title":"Radiation treatment inhibits monocyte entry into the optic nerve head and prevents neuronal damage in a mouse model of glaucoma","volume":"122","author":"Howell","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s13024-018-0303-3","article-title":"Inhibition of monocyte-like cell extravasation protects from neurodegeneration in DBA\/2J glaucoma","volume":"14","author":"Williams","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1002\/glia.22695","article-title":"Mechanosensitive release of adenosine 5\u2032-triphosphate through pannexin channels and mechanosensitive upregulation of pannexin channels in optic nerve head astrocytes: A mechanism for purinergic involvement in chronic strain","volume":"62","author":"Beckel","year":"2014","journal-title":"Glia"},{"key":"ref_174","first-page":"749","article-title":"Astrocytes in the optic nerve head express putative mechanosensitive channels","volume":"21","author":"Choi","year":"2015","journal-title":"Mol. Vis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3109\/02713683.2013.836541","article-title":"From mechanosensitivity to inflammatory responses: New players in the pathology of glaucoma","volume":"39","author":"Krizaj","year":"2014","journal-title":"Curr. Eye Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.1167\/iovs.14-15891","article-title":"Rat, mouse, and primate models of chronic glaucoma show sustained elevation of extracellular ATP and altered purinergic signaling in the posterior eye","volume":"56","author":"Lu","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fncel.2017.00227","article-title":"The P2X7 receptor primes IL-1beta and the NLRP3 inflammasome in astrocytes exposed to mechanical strain","volume":"11","author":"Albalawi","year":"2017","journal-title":"Front. Cell Neurosci."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Astafurov, K., Elhawy, E., Ren, L., Dong, C.Q., Igboin, C., Hyman, L., Griffen, A., Mittag, T., and Danias, J. (2014). Oral microbiome link to neurodegeneration in glaucoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104416"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1038\/s41467-018-05681-9","article-title":"Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12974-016-0558-y","article-title":"Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways","volume":"13","author":"Schlamp","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"5690","DOI":"10.1167\/iovs.10-5248","article-title":"Quantification of the effect of different levels of IOP in the astroglia of the rat retina ipsilateral and contralateral to experimental glaucoma","volume":"51","author":"Ramirez","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/1742-2094-9-92","article-title":"IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma","volume":"9","author":"Gallego","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.1038\/s41598-020-61848-9","article-title":"Time course of bilateral microglial activation in a mouse model of laser-induced glaucoma","volume":"10","author":"Ramirez","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12974-016-0509-7","article-title":"Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat","volume":"13","author":"Sapienza","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1167\/tvst.10.1.22","article-title":"When is a control not a control? Reactive microglia occur throughout the control contralateral pathway of retinal ganglion cell projections in experimental glaucoma","volume":"10","author":"Tribble","year":"2021","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"18810","DOI":"10.1073\/pnas.2009425117","article-title":"Redistribution of metabolic resources through astrocyte networks mitigates neurodegenerative stress","volume":"117","author":"Cooper","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.exer.2010.09.005","article-title":"A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma","volume":"93","author":"Burgoyne","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"E1896","DOI":"10.1073\/pnas.1800165115","article-title":"Normal aging induces A1-like astrocyte reactivity","volume":"115","author":"Clarke","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"107776","DOI":"10.1016\/j.celrep.2020.107776","article-title":"Neurotoxic reactive astrocytes drive neuronal death after retinal injury","volume":"31","author":"Guttenplan","year":"2020","journal-title":"Cell Rep."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"108271","DOI":"10.1016\/j.celrep.2020.108271","article-title":"GLP-1 receptor agonist NLY01 reduces retinal inflammation and neuron death secondary to ocular hypertension","volume":"33","author":"Sterling","year":"2020","journal-title":"Cell Rep."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/s12974-020-01930-1","article-title":"Transgenic inhibition of astroglial NF-kappaB restrains the neuroinflammatory and neurodegenerative outcomes of experimental mouse glaucoma","volume":"17","author":"Yang","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_193","first-page":"296","article-title":"Serum autoantibodies to heat shock proteins in glaucoma patients from Japan and the United States","volume":"108","author":"Wax","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"12085","DOI":"10.1523\/JNEUROSCI.3200-08.2008","article-title":"Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand","volume":"28","author":"Wax","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"8222","DOI":"10.1167\/iovs.12-10076","article-title":"Immunoproteomic analysis of potential serum biomarker candidates in human glaucoma","volume":"53","author":"Tezel","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1167\/iovs.06-0737","article-title":"Accelerated aging in glaucoma: Immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head","volume":"48","author":"Tezel","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1167\/iovs.10-5289","article-title":"Oxidative stress and the regulation of complement activation in human glaucoma","volume":"51","author":"Tezel","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1186\/s12974-018-1346-7","article-title":"Reduced AMPK activation and increased HCAR activation drive anti-inflammatory response and neuroprotection in glaucoma","volume":"15","author":"Inman","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.immuni.2015.02.005","article-title":"Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization","volume":"42","author":"Jha","year":"2015","journal-title":"Immunity"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A breakdown in metabolic reprogramming causes microglia dysfunction in Alzheimer\u2019s Disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell Metab."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1001\/archopht.118.5.666","article-title":"Matrix metalloproteinases and tumor necrosis factor alpha in glaucomatous optic nerve head","volume":"118","author":"Yan","year":"2000","journal-title":"Arch. Ophthalmol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0079-6123(08)01128-X","article-title":"TNF-alpha signaling in glaucomatous neurodegeneration","volume":"173","author":"Tezel","year":"2008","journal-title":"Prog. Brain Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"12633","DOI":"10.1523\/JNEUROSCI.2801-06.2006","article-title":"Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma","volume":"26","author":"Nakazawa","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Roh, M., Zhang, Y., Murakami, Y., Thanos, A., Lee, S.C., Vavvas, D.G., Benowitz, L.I., and Miller, J.W. (2012). Etanercept, a widely used inhibitor of tumor necrosis factor-alpha (TNF-alpha), prevents retinal ganglion cell loss in a rat model of glaucoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040065"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1001\/archopht.124.4.520","article-title":"Minocycline delays death of retinal ganglion cells in experimental glaucoma and after optic nerve transection","volume":"124","author":"Melamed","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1167\/iovs.07-1337","article-title":"Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA\/2J mouse model of glaucoma","volume":"49","author":"Bosco","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/jnc.14070","article-title":"Involvement of microglia in early axoglial alterations of the optic nerve induced by experimental glaucoma","volume":"142","author":"Bordone","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fnmol.2019.00036","article-title":"Inflammasome activation induces pyroptosis in the retina exposed to ocular hypertension injury","volume":"12","author":"Pronin","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1167\/iovs.05-0865","article-title":"Microarray analysis of retinal gene expression in the DBA\/2J model of glaucoma","volume":"47","author":"Steele","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Nikolskaya, T., Nikolsky, Y., Serebryiskaya, T., Zvereva, S., Sviridov, E., Dezso, Z., Rahkmatulin, E., Brennan, R.J., Yankovsky, N., and Bhattacharya, S.K. (2009). Network analysis of human glaucomatous optic nerve head astrocytes. BMC Med. Genom., 2.","DOI":"10.1186\/1755-8794-2-24"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"9944","DOI":"10.1073\/pnas.96.17.9944","article-title":"Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma","volume":"96","author":"Neufeld","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_212","first-page":"365","article-title":"Induction of HLA-DR expression in human lamina cribrosa astrocytes by cytokines and simulated ischemia","volume":"42","author":"Yang","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1006\/exer.1998.0577","article-title":"Enhanced tenascin expression associated with reactive astrocytes in human optic nerve heads with primary open angle glaucoma","volume":"68","author":"Pena","year":"1999","journal-title":"Exp. Eye Res."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1038\/s41467-017-01718-7","article-title":"Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers","volume":"8","author":"Marzeda","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/1742-2094-9-213","article-title":"Transgenic inhibition of astroglial NF-kappaB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis","volume":"9","author":"Brambilla","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"3052","DOI":"10.1242\/jcs.162404","article-title":"NF-kappaB controls axonal regeneration and degeneration through cell-specific balance of RelA and p50 in the adult CNS","volume":"127","author":"Haenold","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuron.2014.11.018","article-title":"NFkappaB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer\u2019s disease","volume":"85","author":"Lian","year":"2015","journal-title":"Neuron"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1126\/science.274.5288.787","article-title":"Suppression of TNF-alpha-induced apoptosis by NF-kappaB","volume":"274","author":"Martin","year":"1996","journal-title":"Science"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/ni0302-221","article-title":"NF-kappaB at the crossroads of life and death","volume":"3","author":"Karin","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/nn1110","article-title":"NF-kappa B functions in synaptic signaling and behavior","volume":"6","author":"Meffert","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"5414","DOI":"10.1523\/JNEUROSCI.2456-10.2011","article-title":"A requirement for nuclear factor-kappaB in developmental and plasticity-associated synaptogenesis","volume":"31","author":"Boersma","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1038\/mt.2009.184","article-title":"Molecular evolution of adeno-associated virus for enhanced glial gene delivery","volume":"17","author":"Koerber","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/mt.2011.62","article-title":"AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa","volume":"19","author":"Dalkara","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"8562","DOI":"10.1167\/iovs.10-6835","article-title":"Hypoxia-regulated retinal glial cell-specific promoter for potential gene therapy in disease","volume":"52","author":"Prentice","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"8044","DOI":"10.1167\/iovs.14-13932","article-title":"A hypoxia-responsive glial cell-specific gene therapy vector for targeting retinal neovascularization","volume":"55","author":"Biswal","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2015.03.022","article-title":"Specific gene expression in mouse cortical astrocytes is mediated by a 1740bp-GFAP promoter-driven combined adeno-associated virus 2\/5\/7\/8\/9","volume":"593","author":"Meng","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"9336","DOI":"10.1523\/JNEUROSCI.3975-14.2015","article-title":"Ascl1 converts dorsal midbrain astrocytes into functional neurons in vivo","volume":"35","author":"Liu","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/s41467-020-14855-3","article-title":"Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington\u2019s disease","volume":"11","author":"Wu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/imr.12541","article-title":"Caspase-8: Regulating life and death","volume":"277","author":"Tummers","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nature09852","article-title":"Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis","volume":"471","author":"Oberst","year":"2011","journal-title":"Nature"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nature09788","article-title":"Caspase signalling controls microglia activation and neurotoxicity","volume":"472","author":"Burguillos","year":"2011","journal-title":"Nature"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"7416","DOI":"10.1074\/jbc.M606721200","article-title":"Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling","volume":"282","author":"Lemmers","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"e716","DOI":"10.1038\/cddis.2013.238","article-title":"Caspase blockade induces RIP3-mediated programmed necrosis in Toll-like receptor-activated microglia","volume":"4","author":"Kim","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.4049\/jimmunol.1302549","article-title":"Cutting edge: Endoplasmic reticulum stress licenses macrophages to produce mature IL-1beta in response to TLR4 stimulation through a caspase-8- and TRIF-dependent pathway","volume":"192","author":"Shenderov","year":"2014","journal-title":"J. Immunol."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Philip, N.H., DeLaney, A., Peterson, L.W., Santos-Marrero, M., Grier, J.T., Sun, Y., Wynosky-Dolfi, M.A., Zwack, E.E., Hu, B., and Olsen, T.M. (2016). Activity of uncleaved caspase-8 controls anti-bacterial immune defense and TLR-induced cytokine production independent of cell death. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005910"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/imr.12284","article-title":"Caspase-8 functions as a key mediator of inflammation and pro-IL-1beta processing via both canonical and non-canonical pathways","volume":"265","author":"Monie","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"11181","DOI":"10.1073\/pnas.1402819111","article-title":"Caspase-8 promotes NLRP1\/NLRP3 inflammasome activation and IL-1beta production in acute glaucoma","volume":"111","author":"Chi","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ajpath.2014.08.025","article-title":"Novel roles for caspase-8 in IL-1beta and inflammasome regulation","volume":"185","author":"Gurung","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1038\/cti.2016.83","article-title":"Caspase-8: Not so silently deadly","volume":"6","author":"Feltham","year":"2017","journal-title":"Clin. Transl. Immunol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/40657","article-title":"Inhibition of death receptor signals by cellular FLIP","volume":"388","author":"Irmler","year":"1997","journal-title":"Nature"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1093\/emboj\/cdf356","article-title":"c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis","volume":"21","author":"Chang","year":"2002","journal-title":"EMBO J."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/cdd.2012.65","article-title":"The flick of a switch: Which death program to choose?","volume":"19","author":"Vandenabeele","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_243","first-page":"pe2","article-title":"The FLIP Side of Life","volume":"258","author":"Silke","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1084\/jem.20051556","article-title":"The c-FLIP-NH2 terminus (p22-FLIP) induces NF-kappaB activation","volume":"203","author":"Golks","year":"2006","journal-title":"J. Exp. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/6\/1372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:10Z","timestamp":1760163010000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/6\/1372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,2]]},"references-count":244,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["cells10061372"],"URL":"https:\/\/doi.org\/10.3390\/cells10061372","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,2]]}}}