Mitochondrial aberrations and ophthalmic diseases

In this review, we comprehensively describe ophthalmic diseases with mitochondrial DNA mutation such as Leber's hereditary optic neuropathy (LHON), progressive external ophthalmoplegia (PEO) and Kearns-Sayre Syndrome (KSS). Ocular involvement is a prominent clinical feature of various mitochondrial diseases as well. The known mitochondrial disorders such as Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Myoclonic epilepsy with ragged-red fibers (MERRF), Mitochondrial neurogastrointestinal encephalopathy (MNGIE) and Neuropathy, ataxia, and retinitis pigmentosa (NARP) exhibiting secondary ophthalmologic manifestations have also been included. In addition, mitochondrial disorders with nuclear gene defects such as Autosomal dominant optic atrophy (ADOA), Autosomal Dominant Optic Atrophy and Cataract (ADOAC), Costeff Optic Atrophy Syndrome (COAS) have also been described. Finally, this review covers ophthalmic diseases with secondary mitochondrial dysfunctions including glaucoma, non-arteritic anterior ischemic optic neuropathy (NAION), diabetic retinopathy (DR) and age-related macular degeneration (AMD). The association of mitochondrial dysfunction in various ophthalmic diseases and ocular manifestations observed in mitochondrial disorders provides a strong evidence for a direct or indirect role of mitochondrial aberrations in ocular diseases and represents a potential therapeutic target. Some of the plausible disease mechanism(s) and therapeutic modalities are also reviewed. Abbreviations: RGCs: Retinal ganglion cells; OXPHOS: Oxidative phosphorylation; ROS: Reactive oxygen species; mtDNA: Mitochondrial DNA; DR: Diabetic retinopathy; AMD: Age-related macular degeneration; LHON: Leber's hereditary optic neuropathy; PEO: Progressive external ophthalmoplegia; COX: Cytochrome c oxidase; CPEO: Chronic Progressive External Opthalmoplegia; KSS: KearnsSayre Syndrome; NAION: Non-arteritic anterior ischemic optic neuropathy; MELAS: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; NGS: Next generation sequencing; MERRF: Myoclonic epilepsy with ragged-red fibers; POLG: Polymerase: DNA directed, gamma; MNGIE: Mitochondrial Neurogastrointestinal encephalomyopathy; NARP: Neurogenic weakness, Ataxia and Retinitis Pigmentosa; LS: Leigh syndrome