{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:45:20Z","timestamp":1793295920628,"version":"4.5.0"},"reference-count":123,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T00:00:00Z","timestamp":1582588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glaucoma is one of the leading causes of irreversible blindness in the world and remains a major public health problem. To date, incomplete knowledge of this disease\u2019s pathophysiology has resulted in current therapies (pharmaceutical or surgical) unfortunately having only a slowing effect on disease progression. Recent research suggests that glaucomatous optic neuropathy is a disease that shares common neuroinflammatory mechanisms with \u201cclassical\u201d neurodegenerative pathologies. In addition to the death of retinal ganglion cells (RGCs), neuroinflammation appears to be a key element in the progression and spread of this disease. Indeed, early reactivity of glial cells has been observed in the retina, but also in the central visual pathways of glaucoma patients and in preclinical models of ocular hypertension. Moreover, neuronal lesions are not limited to retinal structure, but also occur in central visual pathways. This review summarizes and puts into perspective the experimental and clinical data obtained to date to highlight the need to develop neuroprotective and immunomodulatory therapies to prevent blindness in glaucoma patients.<\/jats:p>","DOI":"10.3390\/cells9030535","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T04:18:29Z","timestamp":1582690709000},"page":"535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Glaucoma: A Degenerative Optic Neuropathy Related to Neuroinflammation?"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-9591","authenticated-orcid":false,"given":"St\u00e9phane","family":"M\u00e9lik Parsadaniantz","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3855-9523","authenticated-orcid":false,"given":"Annabelle","family":"R\u00e9aux-le Goazigo","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Sapienza","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6090-0321","authenticated-orcid":false,"given":"Christophe","family":"Habas","sequence":"additional","affiliation":[{"name":"Service de NeuroImagerie, Centre Hospitalier National d\u2019ophtalmologie des Quinze-Vingts, F-75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Baudouin","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, CNRS, Institut de la Vision, 17 rue Moreau, F-75012 Paris, France"},{"name":"Department of Ophthalmology, H\u00f4pital Ambroise Pare, AP HP, F-92100 Boulogne, France"},{"name":"CHNO des Quinze-Vingts, IHU FOReSIGHT, INSERM-DGOS CIC 1423, 28 rue de Charenton, F-75012 Paris, France"},{"name":"Universit\u00e9 Versailles St Quentin en Yvelines, Paris Saclay, F-78180 Montigny-Le-Bretonneux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,25]]},"reference":[{"key":"ref_1","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_2","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_3","doi-asserted-by":"crossref","first-page":"a017269","DOI":"10.1101\/cshperspect.a017269","article-title":"The complex role of neuroinflammation in glaucoma","volume":"4","author":"Soto","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1177\/112067210301303S06","article-title":"Brain changes in glaucoma","volume":"13","author":"Gupta","year":"2003","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3129\/i07-051","article-title":"Should we treat the brain in glaucoma?","volume":"42","author":"Gupta","year":"2007","journal-title":"Can. J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/ICU.0b013e3280895aea","article-title":"Glaucoma as a neurodegenerative disease","volume":"18","author":"Gupta","year":"2007","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S122","DOI":"10.1016\/j.survophthal.2007.08.006","article-title":"What changes can we expect in the brain of glaucoma patients?","volume":"52","author":"Gupta","year":"2007","journal-title":"Surv. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0079-6123(08)01132-1","article-title":"Glaucoma of the brain: A disease model for the study of transsynaptic neural degeneration","volume":"173","author":"Yucel","year":"2008","journal-title":"Prog. Brain Res."},{"key":"ref_11","first-page":"1370","article-title":"Experimental glaucoma and cell size, density, and number in the primate lateral geniculate nucleus","volume":"41","author":"Weber","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1001\/archopht.118.3.378","article-title":"Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma","volume":"118","author":"Yucel","year":"2000","journal-title":"Arch. Ophthalmol."},{"key":"ref_13","first-page":"1791","article-title":"Glaucoma in primates: Cytochrome oxidase reactivity in parvo- and magnocellular pathways","volume":"41","author":"Crawford","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/WNR.0b013e32831d7f82","article-title":"Molecular imaging reveals unique degenerative changes in experimental glaucoma","volume":"20","author":"Imamura","year":"2009","journal-title":"Neuroreport"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1167\/iovs.02-0779","article-title":"Neurochemical correlates of cortical plasticity after unilateral elevated intraocular pressure in a primate model of glaucoma","volume":"44","author":"Lam","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev.neuro.051508.135728","article-title":"Under pressure: Cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy","volume":"35","author":"Nickells","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ejphar.2016.03.064","article-title":"Retinal ganglion cell death in glaucoma: Exploring the role of neuroinflammation","volume":"787","author":"Russo","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/S0166-2236(97)01139-9","article-title":"Reactive astrocytes: Cellular and molecular cues to biological function","volume":"20","author":"Ridet","year":"1997","journal-title":"Trends Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1001\/archopht.1981.03930010635009","article-title":"Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage","volume":"99","author":"Quigley","year":"1981","journal-title":"Arch. Ophthalmol."},{"key":"ref_21","first-page":"425","article-title":"Distribution of glial fibrillary acidic protein in normal and gliotic human retina","volume":"30","author":"Tuccari","year":"1986","journal-title":"Basic Appl. Histochem."},{"key":"ref_22","first-page":"1088","article-title":"Immunohistologic evidence for retinal glial cell changes in human glaucoma","volume":"43","author":"Wang","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.exer.2005.01.012","article-title":"Long-term glial reactivity in rat retinas ipsilateral and contralateral to experimental glaucoma","volume":"81","author":"Kanamori","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/glia.20000","article-title":"Muller cell response to laser-induced increase in intraocular pressure in rats","volume":"47","author":"Woldemussie","year":"2004","journal-title":"Glia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.neuroscience.2005.12.032","article-title":"Muller glial cells express nestin coupled with glial fibrillary acidic protein in experimentally induced glaucoma in the rat retina","volume":"139","author":"Xue","year":"2006","journal-title":"Neuroscience"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/glia.20516","article-title":"Reactive nonproliferative gliosis predominates in a chronic mouse model of glaucoma","volume":"55","author":"Inman","year":"2007","journal-title":"Glia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.brainres.2009.09.029","article-title":"Detection of early neuron degeneration and accompanying glial responses in the visual pathway in a rat model of acute intraocular hypertension","volume":"1303","author":"Zhang","year":"2009","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0166-2236(96)10040-0","article-title":"The Muller cell: A functional element of the retina","volume":"19","author":"Newman","year":"1996","journal-title":"Trends Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/jnr.490420115","article-title":"Coincidence of L-glutamate\/L-aspartate transporter (GLAST) and glutamine synthetase (GS) immunoreactions in retinal glia: Evidence for coupling of GLAST and GS in transmitter clearance","volume":"42","author":"Derouiche","year":"1995","journal-title":"J. Neurosci. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/0169-328X(94)90014-0","article-title":"Marked increase in glutamate-aspartate transporter (GLAST\/GluT-1) mRNA following transient retinal ischemia","volume":"27","author":"Otori","year":"1994","journal-title":"Mol. Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/(SICI)1098-1136(199810)24:2<187::AID-GLIA4>3.0.CO;2-1","article-title":"Localization of p75 neurotrophin receptor in the retina of the adult SD rat: An immunocytochemical study at light and electron microscopic levels","volume":"24","author":"Hu","year":"1998","journal-title":"Glia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.mcn.2008.12.005","article-title":"Inhibition of p75(NTR) in glia potentiates TrkA-mediated survival of injured retinal ganglion cells","volume":"40","author":"Morquette","year":"2009","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.neulet.2009.02.036","article-title":"Immunohistochemical localization of sortilin and p75(NTR) in normal and ischemic rat retina","volume":"454","author":"Xu","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.preteyeres.2009.07.001","article-title":"Cellular signaling and factors involved in M\u00fcller cell gliosis: Neuroprotective and detrimental effects","volume":"28","author":"Bringmann","year":"2009","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.preteyeres.2006.05.003","article-title":"M\u00fcller cells in the healthy and diseased retina","volume":"25","author":"Bringmann","year":"2006","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/jnc.12822","article-title":"Nerve growth factor inhibits osmotic swelling of rat retinal glial (M\u00fcller) and bipolar cells by inducing glial cytokine release","volume":"131","author":"Garcia","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1600-0420.2005.00565.x","article-title":"Neuronal versus glial cell swelling in the ischaemic retina","volume":"83","author":"Bringmann","year":"2005","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1167\/iovs.08-1723","article-title":"Muller cell response to blue light injury of the rat retina","volume":"49","author":"Iandiev","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/(SICI)1098-1136(199708)20:4<299::AID-GLIA3>3.0.CO;2-1","article-title":"Gap junctions equalize intracellular Na+ concentration in astrocytes","volume":"20","author":"Rose","year":"1997","journal-title":"Glia"},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jocn.2010.06.002","article-title":"Gap junction protein connexin43 (GJA1) in the human glaucomatous optic nerve head and retina","volume":"18","author":"Kerr","year":"2011","journal-title":"J. Clin. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/IJG.0b013e31818c6ef6","article-title":"Friend or foe? Resolving the impact of glial responses in glaucoma","volume":"18","author":"Johnson","year":"2009","journal-title":"J. Glaucoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.preteyeres.2011.11.002","article-title":"The molecular basis of retinal ganglion cell death in glaucoma","volume":"31","author":"Almasieh","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1042\/BST0351127","article-title":"Chronic microglial activation and progressive dopaminergic neurotoxicity","volume":"35","author":"Block","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/nn1997","article-title":"Microglia: Active sensor and versatile effector cells in the normal and pathologic brain","volume":"10","author":"Hanisch","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1179\/016164105X49463a","article-title":"Role of microglia in the central nervous system\u2019s immune response","volume":"27","author":"Streit","year":"2005","journal-title":"Neurol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00281-009-0180-5","article-title":"Role of microglia in neuronal degeneration and regeneration","volume":"31","author":"Walter","year":"2009","journal-title":"Semin. Immunopathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.preteyeres.2014.11.004","article-title":"Retinal microglia: Just bystander or target for therapy?","volume":"45","author":"Karlstetter","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/jnr.1104","article-title":"Activated microglia in the human glaucomatous optic nerve head","volume":"64","author":"Yuan","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"ref_52","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_53","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s002210000360","article-title":"An immunohistochemical study of neuronal and glial cell reactions in retinae of rats with experimental glaucoma","volume":"132","author":"Wang","year":"2000","journal-title":"Exp. Brain Res."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1167\/iovs.06-1282","article-title":"Global changes in optic nerve head gene expression after exposure to elevated intraocular pressure in a rat glaucoma model","volume":"48","author":"Johnson","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","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_57","first-page":"911","article-title":"Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia\/reperfusion injury in the rat","volume":"23","author":"Varano","year":"2017","journal-title":"Mol. Vis."},{"key":"ref_58","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_59","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1002\/glia.22715","article-title":"Fractalkine receptor regulates microglial neurotoxicity in an experimental mouse glaucoma model","volume":"62","author":"Wang","year":"2014","journal-title":"Glia"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1172\/JCI29919","article-title":"Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites","volume":"117","author":"Tsou","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_61","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_62","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_63","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_64","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_65","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_66","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/35021228","article-title":"Toll-like receptors in the induction of the innate immune response","volume":"406","author":"Aderem","year":"2000","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/j.1460-9568.2009.06814.x","article-title":"Inactivation of astroglial NF-kappa B promotes survival of retinal neurons following ischemic injury","volume":"30","author":"Dvoriantchikova","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1152\/physrev.00015.2002","article-title":"Molecular Physiology of P2X Receptors","volume":"82","author":"North","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ejphar.2015.03.008","article-title":"P2X7 receptor antagonists protect against N-methyl-d-aspartic acid-induced neuronal injury in the rat retina","volume":"756","author":"Sakamoto","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/cne.10608","article-title":"Neuron-specific distribution of P2X7 purinergic receptors in the monkey retina","volume":"459","author":"Ishii","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/cne.20045","article-title":"Synaptic Localization of P2X7 Receptors in the Rat Retina","volume":"472","author":"Puthussery","year":"2004","journal-title":"J. Comp. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1460-9568.2006.04895.x","article-title":"Evidence for the involvement of purinergic P2X7 receptors in outer retinal processing","volume":"24","author":"Puthussery","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Vessey, K.A., and Fletcher, E.L. (2012). Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029990"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0169-328X(01)00160-7","article-title":"Identification of purinergic receptors in retinal ganglion cells","volume":"92","author":"Marquordt","year":"2001","journal-title":"Mol. Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.neuint.2005.04.022","article-title":"P2X7 receptor-mRNA and -protein in the mouse retina; changes during retinal degeneration in BALBCrds mice","volume":"47","author":"Franke","year":"2005","journal-title":"Neurochem. Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.exer.2010.06.017","article-title":"Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo","volume":"91","author":"Hu","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.neuroscience.2008.08.036","article-title":"Elevated pressure triggers a physiological release of ATP from the retina: Possible role for pannexin hemichannels","volume":"157","author":"Reigada","year":"2008","journal-title":"Neuroscience"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1242\/dev.01855","article-title":"Neuronal death induced by endogenous extracellular ATP in retinal cholinergic neuron density control","volume":"132","author":"Resta","year":"2005","journal-title":"Development"},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.exer.2011.06.020","article-title":"Sustained elevation of extracellular ATP in aqueous humor from humans with primary chronic angle-closure glaucoma","volume":"93","author":"Li","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_81","first-page":"2080","article-title":"P2X7 receptor activation may be involved in neuronal loss in the retinal ganglion cell layer after acute elevation of intraocular pressure in rats","volume":"19","author":"Sugiyama","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.exer.2007.07.016","article-title":"Acute increase of intraocular pressure releases ATP into the anterior chamber","volume":"85","author":"Zhang","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1167\/iovs.12-10968","article-title":"P2X7 receptor activation mediates retinal ganglion cell death in a human retina model of ischemic neurodegeneration","volume":"54","author":"Niyadurupola","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.brainresbull.2019.05.006","article-title":"Potential role of P2X7 receptor in neurodegenerative processes in a murine model of glaucoma","volume":"150","author":"Pintor","year":"2019","journal-title":"Brain Res. Bull."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1111\/j.1460-9568.2007.05528.x","article-title":"Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP","volume":"25","author":"Resta","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/nri1184","article-title":"Signalling pathways of the TNF superfamily: A double-edged sword","volume":"3","author":"Aggarwal","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1167\/iovs.09-4247","article-title":"Tumor necrosis factor-alpha concentrations in the aqueous humor of patients with glaucoma","volume":"51","author":"Sawada","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/IJG.0b013e3181b4cac7","article-title":"Serum cytokine alteration is associated with optic neuropathy in human primary open angle glaucoma","volume":"19","author":"Huang","year":"2010","journal-title":"J. Glaucoma"},{"key":"ref_89","first-page":"1787","article-title":"TNF-alpha and TNF-alpha receptor-1 in the retina of normal and glaucomatous eyes","volume":"42","author":"Tezel","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_90","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_91","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/1098-1136(200010)32:1<42::AID-GLIA40>3.0.CO;2-3","article-title":"Tumor necrosis factor-alpha: A potentially neurodestructive cytokine produced by glia in the human glaucomatous optic nerve head","volume":"32","author":"Yuan","year":"2000","journal-title":"Glia"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/01616412.1996.11740399","article-title":"Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits","volume":"18","author":"Madigan","year":"1996","journal-title":"Neurol. Res."},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1111\/j.1442-9071.2011.02595.x","article-title":"Association of tumour necrosis factor-alpha -308 G\/A polymorphism with primary open-angle glaucoma","volume":"40","author":"Bozkurt","year":"2012","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4110","DOI":"10.1167\/iovs.09-4974","article-title":"Association of polymorphisms of tumor necrosis factor and tumor protein p53 with primary open-angle glaucoma","volume":"51","author":"Fan","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_96","first-page":"290","article-title":"Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA\/2J mouse model of glaucoma","volume":"8","author":"Smith","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.3109\/02713683.2014.990983","article-title":"Ocular hypertension results in retinotopic alterations in the visual cortex of adult mice","volume":"40","author":"Dekeyster","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_98","first-page":"2217","article-title":"Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates","volume":"15","author":"Lam","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.exer.2008.02.004","article-title":"Changes in visual fields and lateral geniculate nucleus in monkey laser-induced high intraocular pressure model","volume":"86","author":"Sasaoka","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"12685","DOI":"10.1038\/s41598-017-12858-7","article-title":"Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes","volume":"7","author":"Mirzaei","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fnagi.2017.00214","article-title":"The Role of Microglia in Retinal Neurodegeneration: Alzheimer\u2019s Disease, Parkinson, and Glaucoma","volume":"9","author":"Ramirez","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1001\/archopht.124.6.853","article-title":"Visual field defects and retinal ganglion cell losses in patients with glaucoma","volume":"124","author":"Harwerth","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/S0002-9394(14)71283-8","article-title":"Lateral geniculate nucleus in glaucoma","volume":"116","author":"Chaturvedi","year":"1993","journal-title":"Am. J. Ophthalmol."},{"key":"ref_104","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_105","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1442-9071.1997.tb01400.x","article-title":"Magnocellular and parvocellular visual pathways are both affected in a macaque monkey model of glaucoma","volume":"25","author":"Vickers","year":"1997","journal-title":"Aust. N. Z. J. Ophthalmol."},{"key":"ref_106","first-page":"3216","article-title":"Atrophy of relay neurons in magno- and parvocellular layers in the lateral geniculate nucleus in experimental glaucoma","volume":"42","author":"Yucel","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"953","DOI":"10.3109\/02713683.2014.884594","article-title":"Dendritic changes in rat visual pathway associated with experimental ocular hypertension","volume":"39","author":"Liu","year":"2014","journal-title":"Curr. Eye Res."},{"key":"ref_108","first-page":"2S24","article-title":"The results of MRI exploration of glaucoma patients: What are the benefits?","volume":"31","author":"Istoc","year":"2008","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3174\/ajnr.A2486","article-title":"Assessment of lateral geniculate nucleus atrophy with 3T MR imaging and correlation with clinical stage of glaucoma","volume":"32","author":"Dai","year":"2011","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1136\/bjo.2008.138172","article-title":"Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging","volume":"93","author":"Gupta","year":"2009","journal-title":"Br. J. Ophthalmol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1167\/iovs.10-5682","article-title":"Automated morphometry of the visual pathway in primary open-angle glaucoma","volume":"52","author":"Hernowo","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Yu, L., Xie, L., Dai, C., Xie, B., Liang, M., Zhao, L., Yin, X., and Wang, J. (2015). Progressive thinning of visual cortex in primary open-angle glaucoma of varying severity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121960"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.acra.2011.01.014","article-title":"Diffusion tensor imaging detects rarefaction of optic radiation in glaucoma patients","volume":"18","author":"Engelhorn","year":"2011","journal-title":"Acad. Radiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1148\/radiol.2522081240","article-title":"Optic nerve and optic radiation neurodegeneration in patients with glaucoma: In vivo analysis with 3-T diffusion-tensor MR imaging","volume":"252","author":"Garaci","year":"2009","journal-title":"Radiology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3174\/ajnr.A2714","article-title":"Voxel-based morphometry and diffusion tensor imaging of the optic pathway in primary open-angle glaucoma: A preliminary study","volume":"33","author":"Zikou","year":"2012","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1093\/brain\/awp119","article-title":"Changes in cortical grey matter density associated with long-standing retinal visual field defects","volume":"132","author":"Boucard","year":"2009","journal-title":"Brain"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3109\/02713683.2012.683506","article-title":"Voxel-based morphometry of the visual-related cortex in primary open angle glaucoma","volume":"37","author":"Li","year":"2012","journal-title":"Curr. Eye Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1002\/hbm.22079","article-title":"Resting-state functional MRI: Functional connectivity analysis of the visual cortex in primary open-angle glaucoma patients","volume":"34","author":"Dai","year":"2013","journal-title":"Hum. Brain Mapp."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Shimazawa, M., Ito, Y., Inokuchi, Y., Yamanaka, H., Nakanishi, T., Hayashi, T., Ji, B., Higuchi, M., Suhara, T., and Imamura, K. (2012). An alteration in the lateral geniculate nucleus of experimental glaucoma monkeys: In vivo positron emission tomography imaging of glial activation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030526"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1186\/s12974-015-0399-0","article-title":"Early pro-inflammatory cytokine elevations in the DBA\/2J mouse model of glaucoma","volume":"12","author":"Wilson","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2174\/1570159X15666170724104305","article-title":"Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases","volume":"16","author":"Rapino","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7869130","DOI":"10.1155\/2019\/7869130","article-title":"Therapeutic Potential of Mesenchymal Stem Cells and Their Secretome in the Treatment of Glaucoma","volume":"2019","author":"Harrell","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"391","DOI":"10.4103\/1673-5374.245465","article-title":"Neuroinflammation as a target for glaucoma therapy","volume":"14","author":"Adornetto","year":"2019","journal-title":"Neural Regen. Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/3\/535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:01:42Z","timestamp":1760173302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/3\/535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,25]]},"references-count":123,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["cells9030535"],"URL":"https:\/\/doi.org\/10.3390\/cells9030535","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,25]]}}}