{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:57Z","timestamp":1787028237611,"version":"build-2736575974"},"reference-count":119,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies, examine genotype-phenotype correlations, and assess novel therapeutic options to improve diagnostic and treatment methodologies. Methods: A systematic literature review was performed in October 2024, utilizing PubMed, Medline, the Cochrane Library, and ClinicalTrials.gov. Search terms encompassed \u201coptic neuropathy\u201d, \u201cgenetic variants\u201d, \u201cLHON\u201d, \u201cDOA\u201d, \u201cglaucoma\u201d, and \u201cmolecular therapies\u201d. Studies were chosen according to established inclusion criteria, concentrating on the genetic and molecular dimensions of optic neuropathies and their therapeutic ramifications. Results: The results indicate that DOA and LHON are mostly associated with the mitochondrial dysfunction resulting from pathogenic variants in nuclear genes, mainly OPA1, and mitochondrial DNA (mtDNA) genes, respectively. Glaucoma, especially its intricate variants, is linked to variants in genes like MYOC, OPTN, and TBK1. Molecular mechanisms, such as oxidative stress and inflammatory modulation, are pivotal in disease progression. Innovative therapeutics, including gene therapy, RNA-based treatments, and antioxidants such as idebenone, exhibit promise for alleviating optic nerve damage and safeguarding vision. Conclusions: Genetic and molecular investigations have markedly enhanced our comprehension of ocular neuropathies. The amalgamation of genetic and phenotypic data is essential for customized medical strategies. Additional research is required to enhance therapeutic strategies and fill the gaps in our understanding of the underlying pathophysiology. This interdisciplinary approach shows potential for enhancing patient outcomes in ocular neuropathies.<\/jats:p>","DOI":"10.3390\/genes15121559","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T03:50:57Z","timestamp":1733111457000},"page":"1559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Insights on the Genetic and Phenotypic Complexities of Optic Neuropathies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"first","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, London NW1 5QH, UK"},{"name":"Eye Clinic, Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francesca","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, London NW1 5QH, UK"},{"name":"Western Eye Hospital, Imperial College Healthcare NHS Trust, London NW1 5QH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2969-8610","authenticated-orcid":false,"given":"Matteo","family":"Capobianco","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1051-876X","authenticated-orcid":false,"given":"Alessandro","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0059-5253","authenticated-orcid":false,"given":"Giuseppe","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi, 95121 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-8361","authenticated-orcid":false,"given":"Mutali","family":"Musa","sequence":"additional","affiliation":[{"name":"Department of Optometry, University of Benin, Benin City 300238, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Barboni","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"},{"name":"Studio Oculistico d\u2019Azeglio, 40123 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. 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