Mitochondria and the eye—manifestations of mitochondrial diseases and their management

Abstract

Historically, distinct mitochondrial syndromes were recognised clinically by their ocular features. Due to their predilection for metabolically active tissue, mitochondrial diseases frequently involve the eye, resulting in a range of ophthalmic manifestations including progressive external ophthalmoplegia, retinopathy and optic neuropathy, as well as deficiencies of the retrochiasmal visual pathway. With the wider availability of genetic testing in clinical practice, it is now recognised that genotype-phenotype correlations in mitochondrial diseases can be imprecise: many classic syndromes can be associated with multiple genes and genetic variants, and the same genetic variant can have multiple clinical presentations, including subclinical ophthalmic manifestations in individuals who are otherwise asymptomatic. Previously considered rare diseases with no effective treatments, considerable progress has been made in our understanding of mitochondrial diseases with new therapies emerging, in particular, gene therapy for inherited optic neuropathies.

Polycystic Ovary Syndrome and Oxidative Stress—From Bench to Bedside

“…Mitochondrial dysfunction is associated with the development of various metabolic diseases. Multiple dysfunctions of the OXPHOS system are associated with clinical manifestations ranging from single lesions in ophthalmological diseases to more extensive lesions or complex multisystem diseases [ 79 , 80 , 81 , 82 ]. Decreased OXPHOS activity was found to be associated with the deficiency of NADH:ubiquinone oxidoreductase—Complex I (CI), the first and largest complex of the OXPHOS system [ 83 ].…”

A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases

“…By mapping the endogenous networks of mitochondrial transfer within the retina, stem cell-derived products could be utilized as mitochondrial delivery vectors to specific retinal cell types. Of particular interest will be rare diseases caused by mutations in the mitochondrial genome (mtDNA) ( 223 ). Another application is the delivery of engineered mitochondria ( 224 , 225 ) to increase the survival of RPE, photoreceptors and other retinal cells with compromised capacity for redox homeostasis ( 226 , 227 ).…”

Hereditary Optic Neuropathies: A Systematic Review on the Interplay between Biomaterials and Induced Pluripotent Stem Cells

“…Moreover, rare optic neuropathies like Leber Hereditary Optic Neuropathy (LHON) and dominant optic atrophy (DOA) are finding increasing awareness in European society with a clear aim to improve patient access to diagnosis, information, and care. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells (RGCs) and axons [2]. Currently, traditional treatments remain incompetent in terms of restoring visual function.…”