{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:39:54Z","timestamp":1792582794815,"version":"4.5.0"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Retinal ganglion cells (RGCs) generally fail to regenerate axons, resulting in irreversible vision loss after optic nerve injury. While many studies have shown that modulating specific genes can enhance RGCs survival and promote optic nerve regeneration, inducing long-distance axon regeneration <jats:italic>in vivo<\/jats:italic> through single-gene manipulation remains challenging. Nevertheless, combined multi-gene therapies have proven effective in significantly enhancing axonal regeneration. At present, research on promoting optic nerve regeneration remains slow, with most studies unable to achieve axonal growth beyond the optic chiasm or reestablish connections with the brain. Future research priorities include directing axonal growth along correct pathways, facilitating synapse formation and myelination, and modifying the inhibitory microenvironment. These strategies are crucial not only for optic nerve regeneration but also for broader applications in central nervous system repair. In this review, we discuss multifactors therapeutic strategies for optic nerve regeneration, offering insights into advancing nerve regeneration research.<\/jats:p>","DOI":"10.3389\/fneur.2024.1526973","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T08:51:44Z","timestamp":1736412704000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Unlocking the potential for optic nerve regeneration over long distances: a multi-therapeutic intervention"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhen-Gang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai-Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Quan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Yin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1167\/14.7.15","article-title":"A formula for human retinal ganglion cell receptive field density as a function of visual field location","volume":"14","author":"Watson","year":"2014","journal-title":"J Vis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.neuron.2019.11.006","article-title":"Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes","volume":"104","author":"Tran","year":"2019","journal-title":"Neuron"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1113\/jphysiol.1974.sp010616","article-title":"The morphological types of ganglion cells of the domestic cat's retina","volume":"240","author":"Boycott","year":"1974","journal-title":"J Physiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1111\/ceo.14259","article-title":"Optic nerve diseases and regeneration: how far are we from the promised land?","volume":"51","author":"Cen","year":"2023","journal-title":"Clin Experiment Ophthalmol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/S1474-4422(22)00174-0","article-title":"Understanding the molecular basis and pathogenesis of hereditary optic neuropathies: towards improved diagnosis and management","volume":"22","author":"Newman","year":"2023","journal-title":"Lancet Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"6064","DOI":"10.1073\/pnas.0909794107","article-title":"Mechanisms of acute axonal degeneration in the optic nerve in vivo","volume":"107","author":"Kn\u00f6ferle","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"101219","DOI":"10.1016\/j.mam.2023.101219","article-title":"Therapeutic strategies for glaucoma and optic neuropathies","volume":"94","author":"Lo","year":"2023","journal-title":"Mol Asp Med"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.neuron.2022.10.028","article-title":"Driving axon regeneration by orchestrating neuronal and non-neuronal innate immune responses via the IFN\u03b3-cGAS-STING axis","volume":"111","author":"Wang","year":"2023","journal-title":"Neuron"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1016\/j.neuron.2022.07.026","article-title":"Live, die, or regenerate? 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