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Glaucomatous optic neuropathy represents the most prevalent form, affecting over 70 million individuals worldwide and causing blindness in nearly 4 million people.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Current Limitations<\/jats:title>\n                    <jats:p>Current treatments targeting elevated intraocular pressure can slow disease progression but cannot restore vision once RGC axons are lost, largely due to regeneration failure in surviving RGCs. This regenerative failure stems not merely from the presence of growth\u2010inhibitory extrinsic factors, but crucially from diminished neuronal\u2010intrinsic regenerative capacity in mature RGCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Mechanistic Insights and Therapeutic Implications<\/jats:title>\n                    <jats:p>This review explores how intrinsic growth barriers and inadequate activation of pro\u2010regenerative genes impede axonal regrowth following injury, and how manipulations of these pathways facilitate axon regeneration and visual recovery in experimental models. Emerging findings suggest that these pro\u2010regenerative molecules capable of modifying the neuronal\u2010intrinsic regenerative capacity of RGCs can also preserve visual function in pre\u2010clinical glaucoma models. Finally, we discuss challenges and future directions for translating these findings into therapies, including gene delivery strategies, remyelination therapeutics, and systems biology\u2010based in silico drug screening approaches aiming to reshape the therapeutic landscape towards regenerative interventions for glaucomatous and other optic neuropathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70800","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:16:42Z","timestamp":1771647402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Regeneration Failure to Functional Restoration: Unlocking the Neuronal\u2010Intrinsic Regenerative Capacity as a Therapeutic Frontier for Optic Neuropathy and Glaucoma"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2845-1915","authenticated-orcid":false,"given":"Emma","family":"Beard","sequence":"first","affiliation":[{"name":"School of Medicine, Pharmacy and Biomedical Science, Faculty of Science and Health University of Portsmouth  Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"El\u2010Bushra","sequence":"additional","affiliation":[{"name":"School of Medicine, Pharmacy and Biomedical Science, Faculty of Science and Health University of Portsmouth  Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2534-7884","authenticated-orcid":false,"given":"Zahra","family":"Kader","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-2936","authenticated-orcid":false,"given":"Yujiao Jennifer","family":"Sun","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0245-9096","authenticated-orcid":false,"given":"Ngan Pan Bennett","family":"Au","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences, School of Veterinary Medicine University of Surrey  Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.860070"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(16)30237\u2010X"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjo.2012.02.003"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214\u2010109X(20)30489\u20107"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.05.013"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433\u2010024\u201002995\u20105"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ogla.2022.08.007"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo\u20102025\u2010328373"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433\u2010019\u20100667\u20109"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2024.3884"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)01289\u20108"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3192"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcjo.2016.07.013"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2024.08.023"},{"key":"e_1_2_15_16_1","volume-title":"Estudios sobre la degeneraci\u00f3n y regeneraci\u00f3n del sistema nervioso: Degeneraci\u00f3n y regeneraci\u00f3n de los nervios","author":"y Cajal S. 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