{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:26:03Z","timestamp":1778631963701,"version":"3.51.4"},"reference-count":132,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Mitochondrial optic neuropathies are a group of optic nerve atrophies exemplified by the two commonest conditions in this group, autosomal dominant optic atrophy (ADOA) and Leber\u2019s hereditary optic neuropathy (LHON). Their clinical features comprise reduced visual acuity, colour vision deficits, centro-caecal scotomas and optic disc pallor with thinning of the retinal nerve fibre layer. The primary aetiology is genetic, with underlying nuclear or mitochondrial gene mutations. The primary pathology is owing to retinal ganglion cell dysfunction and degeneration. There is currently only one approved treatment and no curative therapy is available. In this review we summarise the genetic and clinical features of ADOA and LHON and then examine what new avenues there may be for therapeutic intervention. The therapeutic strategies to manage LHON and ADOA can be split into four categories: prevention, compensation, replacement and repair. Prevention is technically an option by modifying risk factors such as smoking cessation, or by utilising pre-implantation genetic diagnosis, although this is unlikely to be applied in mitochondrial optic neuropathies due to the non-life threatening and variable nature of these conditions. Compensation involves pharmacological interventions that ameliorate the mitochondrial dysfunction at a cellular and tissue level. Replacement and repair are exciting new emerging areas. Clinical trials, both published and underway, in this area are likely to reveal future potential benefits, since new therapies are desperately needed.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>Optic nerve damage leading to loss of vision can be caused by a variety of insults. One group of conditions leading to optic nerve damage is caused by defects in genes that are essential for cells to make energy in small organelles called mitochondria. These conditions are known as mitochondrial optic neuropathies and two predominant examples are called autosomal dominant optic atrophy and Leber\u2019s hereditary optic neuropathy. Both conditions are caused by problems with the energy powerhouse of cells: mitochondria. The cells that are most vulnerable to this mitochondrial malfunction are called retinal ganglion cells, otherwise collectively known as the optic nerve, and they take the electrical impulse from the retina in the eye to the brain. The malfunction leads to death of some of the optic nerve cells, the degree of vision loss being linked to the number of those cells which are impacted in this way. Patients will lose visual acuity and colour vision and develop a central blind spot in their field of vision. There is currently no cure and very few treatment options. New treatments are desperately needed for patients affected by these devastating diseases. New treatments can potentially arise in four ways: prevention, compensation, replacement and repair of the defects. Here we explore how present and possible future treatments might provide hope for those suffering from these conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/26330040211029037","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T22:19:31Z","timestamp":1626733171000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["New avenues for therapy in mitochondrial optic neuropathies"],"prefix":"10.1177","volume":"2","author":[{"given":"Wing Sum Vincent","family":"Ng","sequence":"first","affiliation":[{"name":"School of Medicine, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthieu","family":"Trigano","sequence":"additional","affiliation":[{"name":"Mitochondria and Vision Lab, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Freeman","sequence":"additional","affiliation":[{"name":"Mitochondria and Vision Lab, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Varrichio","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-1722","authenticated-orcid":false,"given":"Dinesh Kumar","family":"Kandaswamy","sequence":"additional","affiliation":[{"name":"Mitochondria and Vision Lab, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Newland","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Brancale","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Rozanowska","sequence":"additional","affiliation":[{"name":"Mitochondria and Vision Lab, School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcela","family":"Votruba","sequence":"additional","affiliation":[{"name":"School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff, CF24 4HQ, Wales, UK; Cardiff Eye Unit, University Hospital of Wales, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"bibr1-26330040211029037","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022567"},{"key":"bibr2-26330040211029037","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2001-2-6-reviews1018"},{"key":"bibr3-26330040211029037","unstructured":"Alberts B, Johnson A, Lewis J, et al. 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