Mitochondrial Dysfunction in the Aging Retina.

Janis T Eells

doi:10.3390/biology8020031

Abstract

Mitochondria are central in retinal cell function and survival and they perform functions that are critical to cell function. Retinal neurons have high energy requirements, since large amounts of ATP are needed to generate membrane potentials and power membrane pumps. Mitochondria over the course of aging undergo a number of changes. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species (ROS) generation and increased numbers of mtDNA mutations. Mitochondria in the neural retina and the retinal pigment epithelium are particularly susceptible to oxidative damage with aging. Many age-related retinal diseases, including glaucoma and age-related macular degeneration, have been associated with mitochondrial dysfunction. Therefore, mitochondria are a promising therapeutic target for the treatment of retinal disease.

Highlights

Mitochondria are central in retinal cell function and survival and they perform functions that are critical to cell function
Recent studies have proposed a model in photoreceptors which glucose from theitchoroidal passes through the pigment epithelium to the retina, where convert to lactate blood passes through the retinal pigment epithelium to the retina, where photoreceptors convert to
Mitochondria are central to retinal cell function and survival and they perform a variety of Mitochondria are central to retinal cell function and survival and they perform a variety of functions critical to cell metabolism, including oxidative phosphorylation, beta-oxidation of fatty acids, functions critical to cell metabolism, including oxidative phosphorylation, beta-oxidation of fatty calcium homeostasis, and the regulation of neuronal excitability [7,8,9,10,11,12,13]

Summary

Retinal Anatomy and Physiology

The fundamental organization of the retina is conserved across vertebrates. The retina contains five major neuronal cell classes (photoreceptors, bipolar cells, amacrine cells, horizontal cells, and retinal ganglion cells) with Müller glial cells and retinal pigment epithelial cells providing metabolic and homeostatic support [1] (Figure 1). Aerobic glycolysis dominates energy production in the photoreceptors, the retina requires both glycolysis and oxidative phosphorylation to initiate vision [4]. This has been demonstrated in studies showing that the responses of neurons downstream of photoreceptors are abolished by inhibiting glycolysis. More phosphorylation oxygen per gram in of tissue than any cell in the with body high [2,5]. This Photoreceptors intense degreeconsume of oxidative their weight inner segments, coupled.

Age-Related Mitochondrial Changes

Age-Related Macular Degeneration

Diabetic Retinopathy

Glaucoma

Conclusions