{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:23:08Z","timestamp":1789068188272,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh"},{"name":"Department of Translational Medicine, University of Ferrara, Ferrara, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber\u2019s hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA\u2019s variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases.<\/jats:p>","DOI":"10.3390\/genes16030347","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T07:49:57Z","timestamp":1742197797000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mitochondrial DNA Pathogenic Variants in Ophthalmic Diseases: A Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Khaled K.","family":"Abu-Amero","sequence":"first","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bashaer","family":"Almadani","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Abualkhair","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2746-0784","authenticated-orcid":false,"given":"Syed","family":"Hameed","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-6951","authenticated-orcid":false,"given":"Altaf A","family":"Kondkar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6575-7931","authenticated-orcid":false,"given":"Andrea","family":"Sollazzo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeli Christy","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-3521","authenticated-orcid":false,"given":"Massimo","family":"Busin","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Zauli","sequence":"additional","affiliation":[{"name":"Research Department, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chandel, N.S. 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