Alpha crystallins in the retinal pigment epithelium and implications for the pathogenesis and treatment of age-related macular degeneration

Background: alpha A- and alpha B crystallins are principal members of the small heat shock protein family and elicit both a cell protective function and a chaperone function. alpha-Crystallins have been found to be prominent proteins in normal and pathological retina emphasizing the importance for in-depth understanding of their function and significance. Scope of review: Retinal pigment epithelial cells (RPE) play a vital role in the pathogenesis of age-related macular degeneration (AMD). This review addresses a number of cellular functions mediated by alpha-crystallins in the retina. Prominent expression of alpha B crystallin in mitochondria may serve to protect cells from oxidative injury, aB crystallin as secretory protein via exosomes can offer neuroprotection to adjacent RPE cells and photoreceptors. The availability of chaperone-containing minipeptides of aB crystallin could prove to be a valuable new tool for therapeutic treatment of retinal disorders. Major conclusions: alpha-Crystallins are expressed in cytosol and mitochondria of RPE cells and are regulated during oxygen-induced retinopathy and during development alpha-Crystallins protect RPE from oxidative-and ER stress-induced injury and autophagy. alpha B-Crystallin is a modulator of angiogenesis and vascular endothelial growth factor. alpha B Crystallin is secreted via exosomal pathway. Minichaperone peptides derived from alpha B Crystallin prevent oxidant induced cell death and have therapeutic potential. General significance: Overall, this review summarizes several novel properties of alpha-crystallins and their relevance to maintaining normal retinal function. In particular, the use of a-crystallin derived peptides is a promising therapeutic strategy to combat retinal diseases such as AMD. This article is part of a Special Issue entitled Crystallin biochemistry in health and disease. (C) 2015 Elsevier B.V. All rights reserved.