Mitochondrial disorders and the eye

Abstract

Purpose of Review Mitochondrial disease is a heterogeneous group of energy metabolism disorders that present across all ages with a wide range of ocular or multi-systemic manifestations. This review focuses on recent progress made toward understanding the various ophthalmologic manifestations of primary mitochondrial diseases and discusses the implications of mitochondrial dysfunction, placing particular emphasis on recent investigations into the pathogenesis and emerging therapies for mitochondrial-based ophthalmologic disorders. Recent Findings Novel pathogenic mitochondrial DNA mutations continue to be detected in diverse ethnic populations for primary mitochondrial ophthalmologic disorders that common affect the optic nerve, retina, and extraocular muscles. Promising antioxidant and gene therapy approaches are being actively investigated to treat these ophthalmologic manifestations, as in Leber Hereditary Optic Neuropathy. Mitochondrial dysfunction is also increasingly implicated in common ophthalmologic disorders of aging, including diabetic retinopathy, age-related macular degeneration, and glaucoma. Several proteins recently recognized to play a role in the mitochondrial oxidative stress response within retinal cells, such as prohibitin and MMP2, may serve as novel biomarkers and therapeutic targets for common ophthalmologic disorders. Therapies that inhibit mitochondrial function and induce apoptosis within tumor cells, such as EDL-155 and curcumin, may offer novel therapeutic agents for ocular neoplasms such as retinoblastoma and uveal melanoma. Summary Primary mitochondrial genetic disease manifestations can involve almost all aspects of the eye. Mitochondrial dysfunction is increasingly recognized as playing a causative role in the common ophthalmologic disorders in aging. This understanding has unleashed a range of emerging therapeutic approaches for mitochondrial-based ophthalmologic disorders directed at optimizing mitochondrial function.

Curcumin Inhibits Neuronal Loss in the Retina and Elevates Ca2+/Calmodulin-Dependent Protein Kinase II Activity in Diabetic Rats

“…[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]33,34,39 In this study, we partially elucidated the molecular mechanisms of cell apoptosis in diabetes-induced rats and demonstrated that curcumin was excellent for treatment. We found that neuronal loss occurred in the retinas of diabetic rats.…”

“…However, researchers have not yet been able to elucidate the mechanisms by which curcumin prevents the progression of diabetic retinopathy. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Although many studies have reported that curcumin rescues retinal neuronal cell cultures from glutamate toxicity, 36,37 researchers have not been able to determine how curcumin treatment ameliorates the diabetes-induced damage to retinal Department of Ophthalmology, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang Province, People's Republic of China. *These two authors contributed equally to the work and therefore should be considered equivalent authors.…”

Ophthalmologic involvement in Leigh syndrome

“…Ophthalmological findings in different genetically verified MIDs have previously been reported by our multidisciplinary team (Gronlund et al 2010). Ophthalmological findings in Leigh syndrome are ptosis, nystagmus, strabismus, reduced visual acuity, retinal pigmentation/dystrophy and optic atrophy (Rose et al 2008;Gronlund et al 2010;Schrier & Falk 2011;Han et al 2015). In addition, non-specific corneal abnormalities and epithelial dysfunction of the ciliary body have been reported (Hayashi et al 2000;Tyni et al 2004).…”

Neuromuscular and Systemic Presentations in Adults: diagnoses beyond MERRF and MELAS

“…Ocular dysfunction is a common manifestation of mitochondrial disorders [58,59]. Both retinitis pigmentosa (RP) [58][59][60][61] and optic atrophy (OA) [58][59][60] are features of several well-documented mitochondrial genotypes.…”

“…Both retinitis pigmentosa (RP) [58][59][60][61] and optic atrophy (OA) [58][59][60] are features of several well-documented mitochondrial genotypes. RP is not uncommon in mtDNA point mutations and mtDNA depletion disorders.…”