Metabolism and Vascular Retinopathies: Current Perspectives and Future Directions

Abstract

The retina is one of the most metabolically active organs in the body. Although it is an extension of the brain, the metabolic needs of the retina and metabolic exchanges between the different cell types in the retina are not the same as that of the brain. Retinal photoreceptors convert most of the glucose into lactate via aerobic glycolysis which takes place in their cytosol, yet there are immense numbers of mitochondria in photoreceptors. The present article is a focused review of the metabolic dysregulation seen in retinopathies with underlying vascular abnormalities with aberrant mitochondrial metabolism and Hypoxia-inducible factor (HIF) dependent pathogenesis. Special emphasis has been paid to metabolic exchanges between different cell types in retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Metabolic similarities between these proliferative retinopathies have been discussed.

Keywords: AMD; DR; HIF; ROP; metabolism; mitochondria; retinal metabolism.

Figure 1

Structure of the retina. Depicted is the structure of the retina displaying layered structure of different cell types. The RPE separates choroidal blood supply from the retina. Müller cells span the whole length of the retina maintaining close metabolic connections between the inner retinal blood vessels and the photoreceptors (rods and cones).

Figure 2

Metabolic basis of retinopathy of prematurity. Hyperoxia downregulates biosynthetic pathways leading to hypovascularized retina in phase 1 of ROP/OIR. Hypovascularized retinas, when exposed to room air in the phase 2 of ROP/OIR, lead to aggressive upregulation of neovascularization in the retina, leading to blindness.

Figure 3

Age-related macular degeneration. There are two types of AMD, dry and wet. In dry-AMD, drusen deposits in the between choriocapllaris and RPE, blocking flow of metabolites and oxygen. In the later stage wet-AMD, hypoxia due to oxygen gradient and HIF stabilization leads to neovascularization and loss of central vision.