{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:12Z","timestamp":1787028552702,"version":"build-2736575974"},"reference-count":97,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["VR210056"],"award-info":[{"award-number":["VR210056"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["455003033521"],"award-info":[{"award-number":["455003033521"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["R01 NS115834"],"award-info":[{"award-number":["R01 NS115834"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Barrow Neurological Foundation","award":["VR210056"],"award-info":[{"award-number":["VR210056"]}]},{"name":"Barrow Neurological Foundation","award":["455003033521"],"award-info":[{"award-number":["455003033521"]}]},{"name":"Barrow Neurological Foundation","award":["R01 NS115834"],"award-info":[{"award-number":["R01 NS115834"]}]},{"name":"US National Institutes of Health (NIH)\/National Institute of Neurological Disorders and Stroke (NINDS)","award":["VR210056"],"award-info":[{"award-number":["VR210056"]}]},{"name":"US National Institutes of Health (NIH)\/National Institute of Neurological Disorders and Stroke (NINDS)","award":["455003033521"],"award-info":[{"award-number":["455003033521"]}]},{"name":"US National Institutes of Health (NIH)\/National Institute of Neurological Disorders and Stroke (NINDS)","award":["R01 NS115834"],"award-info":[{"award-number":["R01 NS115834"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic optic neuropathy (TON) has been regarded a vision-threatening condition caused by either ocular or blunt\/penetrating head trauma, which is characterized by direct or indirect TON. Injury happens during sports, vehicle accidents and mainly in military war and combat exposure. Earlier, we have demonstrated that remote ischemic post-conditioning (RIC) therapy is protective in TON, and here we report that AMPK\u03b11 activation is crucial. AMPK\u03b11 is the catalytic subunit of the heterotrimeric enzyme AMPK, the master regulator of cellular energetics and metabolism. The \u03b11 isoform predominates in immune cells including macrophages (M\u03c6s). Myeloid-specific AMPK\u03b11 KO mice were generated by crossing AMPK\u03b11Flox\/Flox and LysMcre to carry out the study. We induced TON in mice by using a controlled impact system. Mice (mixed sex) were randomized in six experimental groups for Sham (mock); Sham (RIC); AMPK\u03b11F\/F (TON); AMPK\u03b11F\/F (TON+RIC); AMPK\u03b11F\/F LysMCre (TON); AMPK\u03b11F\/F LysMCre (TON+RIC). RIC therapy was given every day (5\u20137 days following TON). Data were generated by using Western blotting (pAMPK\u03b11, ICAM1, Brn3 and GAP43), immunofluorescence (pAMPK\u03b11, cd11b, TMEM119 and ICAM1), flow cytometry (CD11b, F4\/80, CD68, CD206, IL-10 and LY6G), ELISA (TNF-\u03b1 and IL-10) and transmission electron microscopy (TEM, for demyelination and axonal degeneration), and retinal oxygenation was measured by a Unisense sensor system. First, we observed retinal morphology with funduscopic images and found TON has vascular inflammation. H&amp;E staining data suggested that TON increased retinal inflammation and RIC attenuates retinal ganglion cell death. Immunofluorescence and Western blot data showed increased microglial activation and decreased retinal ganglion cell (RGCs) marker Brn3 and axonal regeneration marker GAP43 expression in the TON [AMPK\u03b11F\/F] vs. Sham group, but TON+RIC [AMPK\u03b11F\/F] attenuated the expression level of these markers. Interestingly, higher microglia activation was observed in the myeloid AMPK\u03b11F\/F KO group following TON, and RIC therapy did not attenuate microglial expression. Flow cytometry, ELISA and retinal tissue oxygen data revealed that RIC therapy significantly reduced the pro-inflammatory signaling markers, increased anti-inflammatory macrophage polarization and improved oxygen level in the TON+RIC [AMPK\u03b11F\/F] group; however, RIC therapy did not reduce inflammatory signaling activation in the myeloid AMPK\u03b11 KO mice. The transmission electron microscopy (TEM) data of the optic nerve showed increased demyelination and axonal degeneration in the TON [AMPK\u03b11F\/F] group, and RIC improved the myelination process in TON [AMPK\u03b11F\/F], but RIC had no significant effect in the AMPK\u03b11 KO mice. The myeloid AMPK\u03b11c deletion attenuated RIC induced anti-inflammatory macrophage polarization, and that suggests a molecular link between RIC and immune activation. Overall, these data suggest that RIC therapy provided protection against inflammation and neurodegeneration via myeloid AMPK\u03b11 activation, but the deletion of myeloid AMPK\u03b11 is not protective in TON. Further investigation of RIC and AMPK\u03b11 signaling is warranted in TON.<\/jats:p>","DOI":"10.3390\/ijms252413626","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T04:07:40Z","timestamp":1734667660000},"page":"13626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Remote Ischemic Post-Conditioning (RIC) Mediates Anti-Inflammatory Signaling via Myeloid AMPK\u03b11 in Murine Traumatic Optic Neuropathy (TON)"],"prefix":"10.3390","volume":"25","author":[{"given":"Naseem","family":"Akhter","sequence":"first","affiliation":[{"name":"Department of Biology, Arizona State University, Lake Havasu City, AZ 86403, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Contreras","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Barrow Neurological Institute, St Joseph\u2019s Hospital and Medical Center (SJHMC), Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairaj A.","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Centre for Virology, Hamdard University, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F.","family":"Ducruet","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Barrow Neurological Institute, St Joseph\u2019s Hospital and Medical Center (SJHMC), Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Nasrul","family":"Hoda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Medical Center, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah S.","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Medical Center, Detroit, MI 48202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8575-9937","authenticated-orcid":false,"given":"Laxman D.","family":"Gangwani","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanchan","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Barrow Neurological Institute, St Joseph\u2019s Hospital and Medical Center (SJHMC), Phoenix, AZ 85013, USA"},{"name":"School of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2410-574X","authenticated-orcid":false,"given":"Saif","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Barrow Neurological Institute, St Joseph\u2019s Hospital and Medical Center (SJHMC), Phoenix, AZ 85013, USA"},{"name":"Phoenix Veteran Affairs (VA), Phoenix, AZ 85012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.tjo.2015.01.003","article-title":"Traumatic optic neuropathy\u2014Clinical features and management issues","volume":"5","year":"2015","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/S1474-4422(16)30237-X","article-title":"Diagnosis and clinical features of common optic neuropathies","volume":"15","author":"Biousse","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.ohc.2004.05.008","article-title":"Neuro-ophthalmologic diagnosis and therapy of central nervous system trauma","volume":"17","author":"Levin","year":"2004","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.ajo.2011.02.007","article-title":"Traumatic optic neuropathy: An evolving understanding","volume":"151","author":"Steinsapir","year":"2011","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/ICU.0000000000000198","article-title":"Is there treatment for traumatic optic neuropathy?","volume":"26","author":"Chaon","year":"2015","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_6","first-page":"CD006032","article-title":"Steroids for traumatic optic neuropathy","volume":"2013","author":"Griffiths","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nrneurol.2015.223","article-title":"Remote ischaemic conditioning\u2014A new paradigm of self-protection in the brain","volume":"11","author":"Hess","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1161\/STROKEAHA.112.660373","article-title":"Remote ischemic perconditioning is effective alone and in combination with intravenous tissue-type plasminogen activator in murine model of embolic stroke","volume":"43","author":"Hoda","year":"2012","journal-title":"Stroke"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12975-017-0555-1","article-title":"Chronic remote ischemic conditioning is cerebroprotective and induces vascular remodeling in a VCID model","volume":"9","author":"Khan","year":"2018","journal-title":"Transl. Stroke Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1084\/jem.20171905","article-title":"Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation","volume":"215","author":"Vaibhav","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/01.CIR.74.5.1124","article-title":"Preconditioning with ischemia: A delay of lethal cell injury in ischemic myocardium","volume":"74","author":"Murry","year":"1986","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0140-6736(09)62001-8","article-title":"Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: A randomised trial","volume":"375","author":"Kharbanda","year":"2010","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1161\/STROKEAHA.116.016429","article-title":"RECAST (remote ischemic conditioning after stroke trial) a pilot randomized placebo controlled phase II trial in acute ischemic stroke","volume":"48","author":"England","year":"2017","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1227\/NEU.0000000000000514","article-title":"Phase I clinical trial for the feasibility and safety of remote ischemic conditioning for aneurysmal subarachnoid hemorrhage","volume":"75","author":"Gonzalez","year":"2014","journal-title":"Neurosurgery"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Belforte, N., Sande, P.H., de Zavalia, N., Fernandez, D.C., Silberman, D.M., Chianelli, M.S., and Rosenstein, R.E. (2011). Ischemic tolerance protects the rat retina from glaucomatous damage. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023763"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1167\/iovs.08-3344","article-title":"Retinal neuroprotection against ischemia-reperfusion damage induced by postconditioning","volume":"50","author":"Fernandez","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s12017-020-08631-1","article-title":"Remote ischemic post-conditioning therapy is protective in mouse model of traumatic optic neuropathy","volume":"23","author":"Nadeem","year":"2021","journal-title":"NeuroMol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrneurol.2017.13","article-title":"The far-reaching scope of neuroinflammation after traumatic brain injury","volume":"13","author":"Simon","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/brain\/aws322","article-title":"Inflammation and white matter degeneration persist for years after a single traumatic brain injury","volume":"136","author":"Johnson","year":"2013","journal-title":"Brain"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/nan.12008","article-title":"The neuroinflammatory response in humans after traumatic brain injury","volume":"39","author":"Smith","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.tins.2015.08.002","article-title":"Priming the inflammatory pump of the CNS after traumatic brain injury","volume":"38","author":"Witcher","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1523\/JNEUROSCI.2405-14.2015","article-title":"CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury","volume":"35","author":"Morganti","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.neuron.2017.07.010","article-title":"Neuroimmunology of traumatic brain injury: Time for a paradigm shift","volume":"95","author":"Jassam","year":"2017","journal-title":"Neuron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.nbd.2014.08.011","article-title":"Dynamic changes in pro-and anti-inflammatory cytokines in microglia after PPAR-\u03b3 agonist neuroprotective treatment in the MPTPp mouse model of progressive Parkinson\u2019s disease","volume":"71","author":"Pisanu","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.expneurol.2015.08.018","article-title":"Microglia in the TBI brain: The good, the bad, and the dysregulated","volume":"275","author":"Loane","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1089\/neu.2015.4268","article-title":"Microglial\/macrophage polarization dynamics following traumatic brain injury","volume":"33","author":"Kumar","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1038\/jcbfm.2013.146","article-title":"Microglia\/macrophage polarization dynamics in white matter after traumatic brain injury","volume":"33","author":"Wang","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbi.2016.07.158","article-title":"NOX2 drives M1-like microglial\/macrophage activation and neurodegeneration following experimental traumatic brain injury","volume":"58","author":"Kumar","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1073\/pnas.1501441112","article-title":"HDAC inhibition prevents white matter injury by modulating microglia\/macrophage polarization through the GSK3\u03b2\/PTEN\/Akt axis","volume":"112","author":"Wang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nn.2923","article-title":"Heterogeneity of CNS myeloid cells and their roles in neurodegeneration","volume":"14","author":"Prinz","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/imm.12233","article-title":"Inflammation in neurodegenerative diseases\u2014An update","volume":"142","author":"Amor","year":"2014","journal-title":"Immunology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Italiani, P., and Boraschi, D. (2014). From monocytes to M1\/M2 macrophages: Phenotypical vs. functional differentiation. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00514"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Koh, Y.-C., Yang, G., Lai, C.-S., Weerawatanakorn, M., and Pan, M.-H. (2018). Chemopreventive effects of phytochemicals and medicines on M1\/M2 polarized macrophage role in inflammation-related diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082208"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Viola, A., Munari, F., S\u00e1nchez-Rodr\u00edguez, R., Scolaro, T., and Castegna, A. (2019). The metabolic signature of macrophage responses. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01462"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/cr.2015.68","article-title":"Metabolic reprogramming in macrophages and dendritic cells in innate immunity","volume":"25","author":"Kelly","year":"2015","journal-title":"Cell Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.celrep.2016.09.008","article-title":"Mitochondrial dysfunction prevents repolarization of inflammatory macrophages","volume":"17","author":"Baardman","year":"2016","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: Guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1002\/cbin.10915","article-title":"Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism","volume":"42","author":"Ke","year":"2018","journal-title":"Cell Biol. Int."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dugan, L.L., You, Y.-H., Ali, S.S., Diamond-Stanic, M., Miyamoto, S., DeCleves, A.-E., Andreyev, A., Quach, T., Ly, S., and Shekhtman, G. (2013). AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J. Clin. Investig., 4888\u20134899.","DOI":"10.1172\/JCI66218"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1038\/s41423-021-00790-w","article-title":"Activation of AMPK\u03b11 is essential for regulatory T cell function and autoimmune liver disease prevention","volume":"18","author":"Zhu","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1111\/jcmm.13978","article-title":"AMPK\u03b12 knockout enhances tumour inflammation through exacerbated liver injury and energy deprivation-associated AMPK\u03b11 activation","volume":"23","author":"Qiu","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hayes, H.V., Wolfe, V., O\u2019Connor, M., Levinsky, N.C., Piraino, G., and Zingarelli, B. (2021). Deficiency of AMPK\u03b11 exacerbates intestinal injury and remote acute lung injury in mesenteric ischemia and reperfusion in mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189911"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9142","DOI":"10.1167\/iovs.11-8041","article-title":"Roles of AMP-activated protein kinase in diabetes-induced retinal inflammation","volume":"52","author":"Kubota","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10475","DOI":"10.1073\/pnas.1802724115","article-title":"Stimulation of AMPK prevents degeneration of photoreceptors and the retinal pigment epithelium","volume":"115","author":"Xu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.04.005","article-title":"Metabolic pathways in immune cell activation and quiescence","volume":"38","author":"Pearce","year":"2013","journal-title":"Immunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jneuroim.2014.10.006","article-title":"Inhibition of adenosine kinase attenuates inflammation and neurotoxicity in traumatic optic neuropathy","volume":"277","author":"Ahmad","year":"2014","journal-title":"J. Neuroimmunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jneuroim.2013.09.015","article-title":"Potential role of A2A adenosine receptor in traumatic optic neuropathy","volume":"264","author":"Ahmad","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e126747","DOI":"10.1172\/jci.insight.126747","article-title":"Blood-retina barrier failure and vision loss in neuron-specific degeneration","volume":"4","author":"Ivanova","year":"2019","journal-title":"JCI Insight"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Tong, N., Zhang, Z., Zhang, W., Qiu, Y., Gong, Y., Yin, L., Qiu, Q., and Wu, X. (2013). Diosmin alleviates retinal edema by protecting the blood-retinal barrier and reducing retinal vascular permeability during ischemia\/reperfusion injury. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061794"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tong, J., Kedar, S., Ghate, D., and Gu, L. (2019). Indirect traumatic optic neuropathy induced by primary blast: A fluid\u2013structure interaction study. J. Biomech. Eng., 141.","DOI":"10.1115\/1.4043668"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Buys, E.S., Ko, Y.-C., Alt, C., Hayton, S.R., Jones, A., Tainsh, L.T., Ren, R., Giani, A., Clert\u00e9, M., and Abernathy, E. (2013). Soluble guanylate cyclase \u03b11\u2013deficient mice: A novel murine model for primary open angle glaucoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060156"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1167\/iovs.12-11491","article-title":"Effect of nitric oxide on anterior segment physiology in monkeys","volume":"54","author":"Heyne","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"9438","DOI":"10.1167\/iovs.11-7839","article-title":"eNOS, a pressure-dependent regulator of intraocular pressure","volume":"52","author":"Stamer","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1242\/dev.129.2.467","article-title":"Brn3b\/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth","volume":"129","author":"Wang","year":"2002","journal-title":"Development"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chung, D., Shum, A., and Caraveo, G. (2020). GAP-43 and BASP1 in axon regeneration: Implications for the treatment of neurodegenerative diseases. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.567537"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13024-021-00459-y","article-title":"Neuroprotection by Wld S depends on retinal ganglion cell type and age in glaucoma","volume":"16","author":"Risner","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/sj.eye.6701571","article-title":"Traumatic optic neuropathy","volume":"18","author":"Sarkies","year":"2004","journal-title":"Eye"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Saggu, S.K., Chotaliya, H.P., Blumbergs, P.C., and Casson, R.J. (2010). Wallerian-like axonal degeneration in the optic nerve after excitotoxic retinal insult: An ultrastructural study. BMC Neurosci., 11.","DOI":"10.1186\/1471-2202-11-97"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Shu, D.Y., Chaudhary, S., Cho, K.-S., Lennikov, A., Miller, W.P., Thorn, D.C., Yang, M., and McKay, T.B. (2023). Role of oxidative stress in ocular diseases: A balancing act. Metabolites, 13.","DOI":"10.3390\/metabo13020187"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Tuxworth, R.I., Taylor, M.J., Martin Anduaga, A., Hussien-Ali, A., Chatzimatthaiou, S., Longland, J., Thompson, A.M., Almutiri, S., Alifragis, P., and Kyriacou, C.P. (2019). Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration. Brain Commun., 1.","DOI":"10.1093\/braincomms\/fcz005"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Giacci, M.K., Bartlett, C.A., Huynh, M., Kilburn, M.R., Dunlop, S.A., and Fitzgerald, M. (2018). Three dimensional electron microscopy reveals changing axonal and myelin morphology along normal and partially injured optic nerves. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22361-2"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1523\/JNEUROSCI.14-07-04368.1994","article-title":"Axotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats","volume":"14","author":"Berkelaar","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1167\/iovs.18-24096","article-title":"RGC neuroprotection following optic nerve trauma mediated by intranasal delivery of amnion cell secretome","volume":"59","author":"Grinblat","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1167\/iovs.19-26683","article-title":"Tau is involved in death of retinal ganglion cells of rats from optic nerve crush","volume":"60","author":"Oku","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.cmet.2011.11.013","article-title":"Orchestration of metabolism by macrophages","volume":"15","author":"Biswas","year":"2012","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.bbrc.2009.09.017","article-title":"Activation of AMP-activated protein kinase (AMPK) inhibits fatty acid synthesis in bovine mammary epithelial cells","volume":"390","author":"McFadden","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1167\/iovs.09-3717","article-title":"Secondary retinal ganglion cell death and the neuroprotective effects of the calcium channel blocker lomerizine","volume":"50","author":"Fitzgerald","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_68","first-page":"975","article-title":"Optic nerve transection in monkeys may result in secondary degeneration of retinal ganglion cells","volume":"42","author":"Quigley","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/35067570","article-title":"Plasticity of motor systems after incomplete spinal cord injury","volume":"2","author":"Raineteau","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jneumeth.2016.06.018","article-title":"Neuroinflammation in animal models of traumatic brain injury","volume":"272","author":"Chiu","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/ana.22455","article-title":"Inflammation after trauma: Microglial activation and traumatic brain injury","volume":"70","author":"Ramlackhansingh","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/brain\/awp264","article-title":"Stereology of cerebral cortex after traumatic brain injury matched to the Glasgow outcome score","volume":"133","author":"Maxwell","year":"2010","journal-title":"Brain"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"584","DOI":"10.4049\/jimmunol.1401024","article-title":"Adenosine 5\u2032-monophosphate\u2013activated protein kinase regulates IL-10\u2013mediated anti-inflammatory signaling pathways in macrophages","volume":"194","author":"Zhu","year":"2015","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1189\/jlb.0313157","article-title":"AMPK\u03b11 deficiency amplifies proinflammatory myeloid APC activity and CD40 signaling","volume":"94","author":"Carroll","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1167\/iovs.18-24431","article-title":"Tumor necrosis factor inhibition in the acute management of traumatic optic neuropathy","volume":"59","author":"Brian","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11481-012-9347-2","article-title":"Roles of activated microglia in hypoxia induced neuroinflammation in the developing brain and the retina","volume":"8","author":"Kaur","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"16431","DOI":"10.1523\/JNEUROSCI.2119-15.2015","article-title":"Role of IL-10 in resolution of inflammation and functional recovery after peripheral nerve injury","volume":"35","author":"Mietto","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_79","first-page":"7301","article-title":"IL-10 inhibits retinal pigment epithelium cell proliferation and migration through regulation of VEGF in rhegmatogenous retinal detachment","volume":"17","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.ajpath.2019.12.006","article-title":"Intercellular adhesion molecule 1 functions as an efferocytosis receptor in inflammatory macrophages","volume":"190","author":"Wiesolek","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tan Chun Rong, A., Ma, Y., Appukuttan, B., Lower, K., Lumsden, A.L., Michael, M., Smith, J.R., and Ashander, L.M. (2024). Brief Research Report: ETS-1 blockade increases ICAM-1 expression in activated human retinal endothelial cells. Front. Ophthalmol., 4.","DOI":"10.3389\/fopht.2024.1384428"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0079-6123(08)01128-X","article-title":"TNF-\u03b1 signaling in glaucomatous neurodegeneration","volume":"173","author":"Tezel","year":"2008","journal-title":"Prog. Brain Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/med.10001","article-title":"Inhibition of LFA-1\/ICAM-1 and VLA-4\/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases","volume":"22","author":"Anderson","year":"2002","journal-title":"Med. Res. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.brainres.2008.02.090","article-title":"Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia\/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats","volume":"1209","author":"Cheng","year":"2008","journal-title":"Brain Res."},{"key":"ref_85","unstructured":"Graymore, C.N. (1965). Relationships between visual function and metabolism. Biochemistry of the Eye, Academic Press."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1001\/archopht.1964.00970020794009","article-title":"Retinal oxygen utilization measured by hyperbaric blackout","volume":"72","author":"Anderson","year":"1964","journal-title":"Arch. Ophthalmol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"463","DOI":"10.22462\/07.08.2018.12","article-title":"Benefit of hyperbaric oxygen therapy treatment in direct traumatic optic neuropathy: Case report","volume":"45","author":"Hsieh","year":"2018","journal-title":"Undersea Hyperb. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1007\/s00417-021-05208-x","article-title":"The retinal vasculature pathophysiological changes in vision recovery after treatment for indirect traumatic optic neuropathy patients","volume":"259","author":"Gao","year":"2021","journal-title":"Graefe\u2019s Arch. Clin. Exp. Ophthalmol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.freeradbiomed.2003.11.032","article-title":"The biochemistry of nitric oxide, nitrite, and hemoglobin: Role in blood flow regulation","volume":"36","author":"Gladwin","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1167\/iovs.08-3267","article-title":"Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in naive and optic nerve\u2013injured retinas","volume":"50","author":"Agudo","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_91","first-page":"147","article-title":"Regeneration of axons in the visual system","volume":"26","author":"Berry","year":"2008","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1089\/ars.2015.6260","article-title":"Nitrite confers preconditioning and cytoprotection after ischemia\/reperfusion injury through the modulation of mitochondrial function","volume":"23","author":"Shiva","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1161\/CIRCULATIONAHA.115.018935","article-title":"SIRT3\u2013AMP-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction","volume":"133","author":"Lai","year":"2016","journal-title":"Circulation"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1161\/ATVBAHA.111.243980","article-title":"\u03b11AMP-activated protein kinase mediates vascular protective effects of exercise","volume":"32","author":"Jansen","year":"2012","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1167\/iovs.18-24773","article-title":"A Controlled Impact of Optic Nerve as a New Model of Traumatic Optic Neuropathy in Mouse","volume":"59","author":"Ibrahim","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Samra, Y.A., Kira, D., Rajpurohit, P., Mohamed, R., Owen, L.A., Shakoor, A., Kim, I.K., DeAngelis, M.M., Sheibani, N., and Al-Shabrawey, M. (2021). Implication of N-Methyl-d-Aspartate Receptor in Homocysteine-Induced Age-Related Macular Degeneration. Int. J. Mol. Sci., 22.","DOI":"10.21203\/rs.3.rs-481688\/v1"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.4049\/jimmunol.1601948","article-title":"Activation of myeloid TLR4 mediates T lymphocyte polarization after traumatic brain injury","volume":"198","author":"Braun","year":"2017","journal-title":"J. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13626\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:55:55Z","timestamp":1760115355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,19]]},"references-count":97,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413626"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413626","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,19]]}}}