{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:34:53Z","timestamp":1792197293045,"version":"4.4.0"},"reference-count":127,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570849"],"award-info":[{"award-number":["81570849"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515011413"],"award-info":[{"award-number":["2020A1515011413"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The retinal ganglion cells (RGCs) are the sole output neurons that connect information from the retina to the brain. Optic neuropathies such as glaucoma, trauma, inflammation, ischemia and hereditary optic neuropathy can cause RGC loss and axon damage, and lead to partial or total loss of vision, which is an irreversible process in mammals. The accurate diagnoses of optic neuropathies are crucial for timely treatments to prevent irrevocable RGCs loss. After severe ON damage in optic neuropathies, promoting RGC axon regeneration is vital for restoring vision. Clearance of neuronal debris, decreased intrinsic growth capacity, and the presence of inhibitory factors have been shown to contribute to the failure of post\u2010traumatic CNS regeneration. Here, we review the current understanding of manifestations and treatments of various common optic neuropathies. We also summarise the current known mechanisms of RGC survival and axon regeneration in mammals, including specific intrinsic signalling pathways, key transcription factors, reprogramming genes, inflammation\u2010related regeneration factors, stem cell therapy, and combination therapies. Significant differences in RGC subtypes in survival and regenerative capacity after injury have also been found. Finally, we highlight the developmental states and non\u2010mammalian species that are capable of regenerating RGC axons after injury, and cellular state reprogramming for neural repair.<\/jats:p>","DOI":"10.1111\/ceo.14259","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T08:54:16Z","timestamp":1686819256000},"page":"627-641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Optic nerve diseases and regeneration: How far are we from the promised land?"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3876-0606","authenticated-orcid":false,"given":"Ling\u2010Ping","family":"Cen","sequence":"first","affiliation":[{"name":"Department of Neuro\u2010Ophthalmology Joint Shantou International Eye Centre of Shantou University and The Chinese University of Hong Kong  Shantou Guangdong China"},{"name":"Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4796-3894","authenticated-orcid":false,"given":"Kevin K.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, The Miami Project to Cure Paralysis University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-4246","authenticated-orcid":false,"given":"Kowk\u2010Fai","family":"So","sequence":"additional","affiliation":[{"name":"Guangzhou\u2010HongKong\u2010Macau Institute of CNS Regeneration Jinan University  Guangzhou China"},{"name":"Aier School of Ophthalmology Changsha Aier Hospital of Ophthalmology  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.19.030196.001445"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal5060"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52903-9.00012-1"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.16-0428"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.081224"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220624"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.831062"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30237-X"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00200-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00066.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70259-X"},{"issue":"8","key":"e_1_2_7_14_1","first-page":"4025","article-title":"Astrocyte\u2010microglia interaction drives evolving neuromyelitis optica lesion","volume":"130","author":"Chen T","year":"2020","journal-title":"J Clin Invest"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2021.01.004"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31469-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101136"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8183"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232416038"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112911"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1413352"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2016-0027-RS"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijo.IJO_1681_20"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19052718"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19053092"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.12515"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.06.038"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10101538"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000314"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0b013e3182901969"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092653"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(22)00174-0"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2010.11.002"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-020-01428-3"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-013-0389-5"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6701571"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/08820539409060016"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.860070"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2020.10.038"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2013-0003"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.01.002"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01534.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-01783-7"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-13-04186.1996"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.02.001"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.07.002"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-96107-y"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17841"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.25.6.389.14233"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh382"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207523"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.16.7287"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1161566"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.021"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20934"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31960-7"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-vision-022720-094953"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0001-8"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2022.102284"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.11.006"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.017"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.05.035"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0292"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5603-11.2012"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2975-4"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.12.036"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27593"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.105"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2015.12.006"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910702117"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-12-04615.2000"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-06-02284.2003"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1423221112"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0791"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1701"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5511-12.2013"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017282118"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2113751119"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2021.113711"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1326"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91047-9"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a001867"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2011.11.002"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24573"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1159\/000514441"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000777"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1894"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.5.1632"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302791"},{"issue":"3","key":"e_1_2_7_90_1","first-page":"760","article-title":"CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters","volume":"40","author":"Cui Q","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.12.027"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.12.024"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90608"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.04.028"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.08.013"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4354"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113953109"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600407"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.147"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.1038\/416636a"},{"key":"e_1_2_7_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3070"},{"key":"e_1_2_7_102_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666181031102829"},{"key":"e_1_2_7_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2019.146555"},{"key":"e_1_2_7_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(02)00035-0"},{"key":"e_1_2_7_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107863"},{"key":"e_1_2_7_106_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13045"},{"key":"e_1_2_7_107_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0110722"},{"key":"e_1_2_7_108_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2812"},{"issue":"5","key":"e_1_2_7_109_1","first-page":"382","article-title":"Neural stem cell\u2010based intraocular administration of pigment epithelium\u2010derived factor promotes retinal ganglion cell survival and axon regeneration after optic nerve crush injury in rat: An experimental study","volume":"41","author":"Zhang WMM","year":"2016","journal-title":"Iran J Med Sci"},{"key":"e_1_2_7_110_1","first-page":"2658","article-title":"Adult mice transplanted with embryonic retinal progenitor cells: new approach for repairing damaged optic nerves","volume":"18","author":"Cho JH","year":"2012","journal-title":"Mol Vis"},{"key":"e_1_2_7_111_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.6.3.4"},{"key":"e_1_2_7_112_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20515"},{"key":"e_1_2_7_113_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119449109"},{"key":"e_1_2_7_114_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10594"},{"key":"e_1_2_7_115_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4340-10.2010"},{"key":"e_1_2_7_116_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05230.x"},{"key":"e_1_2_7_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.10.025"},{"key":"e_1_2_7_118_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2015.51"},{"key":"e_1_2_7_119_1","doi-asserted-by":"publisher","DOI":"10.1089\/089771504774129946"},{"key":"e_1_2_7_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2006.10.005"},{"key":"e_1_2_7_121_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh706"},{"key":"e_1_2_7_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.06.022"},{"key":"e_1_2_7_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.05.013"},{"key":"e_1_2_7_124_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33799-4"},{"key":"e_1_2_7_125_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01289-0"},{"key":"e_1_2_7_126_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2020.7039"},{"key":"e_1_2_7_127_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1651"},{"key":"e_1_2_7_128_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.178012"}],"container-title":["Clinical &amp; Experimental Ophthalmology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ceo.14259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T06:57:48Z","timestamp":1692082668000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ceo.14259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":127,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1111\/ceo.14259"],"URL":"https:\/\/doi.org\/10.1111\/ceo.14259","archive":["Portico"],"relation":{},"ISSN":["1442-6404","1442-9071"],"issn-type":[{"value":"1442-6404","type":"print"},{"value":"1442-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]},"assertion":[{"value":"2023-01-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}