Claudia Fossataro^1,2*, Maria Cristina Savastano^1,2, Alfonso Savastano^1,2, Riccardo Sadun^1,2, Valentina Cestrone^1,2, Raphael Kilian³ and Stanislao Rizzo^1,2,4

¹Ophthalmology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
²Ophthalmology Unit, Catholic University of the Sacred Heart, Rome, Italy
³Ophthalmology Unit, University of Verona, Verona, Italy
⁴CNR Neuroscience Institute, Pisa, Italy

*Corresponding Author: Claudia Fossataro, Ophthalmology Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

Received: April 05, 2023; Published: May 25, 2023

Abstract

Mitochondria represent the powerhouse of the eukaryotic cells, being responsible of energy production and cell survival. The retina, in particular retinal ganglion cells and photoreceptors, which requires great amount of energy to perform daily activity, have a strong dependence on mitochondria function. In mitochondria diseases, the retina and optic disc are affected, with the typical manifestations of tapeto-retinal degeneration and optic atrophy. Leber hereditary optic neuropathy (LHON) is the most popular mitochondrial retinopathy, with bilateral involvement, characterized by vascular and nervous retinal impairment. In the acute phase the retinal nerve fibers (RNFL) swelling is typically reported, which is later substituted by a RNFL thinning, corresponding to enlargement of centrocecal scotoma and vision impairment. Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, whose diagnosis is usually made accidentally at a follow up visit. The characteristic aspect of fundus is almost similar to LHON. The natural course could consider a steady situation, a steep worsening or a slow and progressive evolution.  In chronic progressive external ophthalmoplegia (CPEO) the posterior segment of the eye is infrequently involved, while the extraocular muscles are the typical targets, leading to ptosis, ocular motility impairment and diplopia. Although many nuclear genes could be responsible of CPEO, a sporadic single deletion in the mtDNA is the most common finding. The typical diagnosis is made following a skeletal muscle biopsy, revealing the characteristic feature “"ragged red fibers". CPEO may show an extremely mild phenotype or being part of a more severe condition, defined Kearns – Sayre syndrome (KSS). The acronym NARP refers to the triad, neurogenic muscle weakness, ataxia and retinitis pigmentosa, which could be found isolated or associated with a severe encephalopathy in the context of maternally inherited Leigh syndrome (MILS). Nowadays, the only approved therapy is the Idebenone, for the treatment of young and adult patients suffering from LHON.

 Keywords: Mitochondrial Retinopathies; Leber Hereditary Optic Neuropathy; Autosomal Dominant Optic Atrophy; Chronic Progressive External Ophthalmoplegia; Neurogenic Muscle Weakness; Ataxia And Retinitis Pigmentosa; Idebenone

References

1. N Howell., et al. “Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees”. American Journal of Human Genetics5 (1991): 939-950.
2. K Huoponen., et al. “A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy”. American Journal of Human Genetics6 (1991): 1147-1153.
3. DR Johns., et al. “An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy”. Biochemical and Biophysical Research Communications 3 (1997): 1551-1557.
4. D Mackey and N Howell. “A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology”. American Journal of Human Genetics6 (1992): 1218-1228.
5. D C Wallace., et al. “Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy”. Science4884 (1988): 1427-1430.
6. P Yu-Wai-Man., et al. “Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies”. Progress in Retinal and Eye Research2 (2011): 81-114.
7. PA Quiros., et al. “Colour vision defects in asymptomatic carriers of the Leber’s hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study”. British Journal of Ophthalmology2 (2006): 150-153.
8. AA Sadun., et al. “Subclinical carriers and conversions in Leber hereditary optic neuropathy: a prospective psychophysical study”. Transactions of the American Ophthalmological Society 104 (2006): 51-61.
9. J A Fraser., et al. “The neuro-ophthalmology of mitochondrial disease”. Survey on Ophthalmology4 (2010): 299-334.
10. M A Kirkman., et al. “Gene-environment interactions in Leber hereditary optic neuropathy”. Brain 9 (2010): 2317-2326.
11. V Carelli., et al. “Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion”. Brain 3 (2016): e17.
12. M Ferré., et al. “Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations”. Human Mutation7 (2009): E692-705.
13. P A Williams., et al. “Opa1 deficiency in a mouse model of dominant optic atrophy leads to retinal ganglion cell dendropathy”. Brain10 (2010): 2942-2951.
14. L B Kline and J S Glaser. “Dominant optic atrophy. The clinical profile”. Archives of Ophthalmology9 (1979): 1680-1686.
15. M Votruba., et al. “Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy”. Archives of Ophthalmology3 (1998): 351-358.
16. D Eliott., et al. “Visual prognosis in autosomal dominant optic atrophy (Kjer type)”. American Journal of Ophthalmology3 (1993): 360-367.
17. S DiMauro and C Garone. “Historical perspective on mitochondrial medicine”. Developmental Disabilities Research Reviews 2 (2010): 106-113.
18. AJ Barkovich., et al. “Mitochondrial disorders: analysis of their clinical and imaging characteristics”. AJNR American Journal of Neuroradiology5 (1993): 1119-1137.
19. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=232006

Citation

Citation: Claudia Fossataro., et al. “Eye and Mitochondrial Diseases".Acta Scientific Ophthalmology 6.6 (2023): 07-09.

Copyright

Copyright: © 2023 Claudia Fossataro., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.