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

• Published in: Biochimica et biophysica acta Vol. 1860; no. 1; pp. 258 - 268
• Main Authors: Kannan, Ram, Sreekumar, Parameswaran G., Hinton, David R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2016
• Subjects: alpha-Crystallins - chemistry; alpha-Crystallins - metabolism; alpha-Crystallins - therapeutic use; Angiogenesis; Animals; Apoptosis; autophagy; Crystallins; cytosol; epithelial cells; epithelium; Exosomes; heat shock proteins; Humans; macular degeneration; Macular Degeneration - drug therapy; Minichaperone peptide; mitochondria; Molecular Chaperones - chemistry; Molecular Chaperones - therapeutic use; neuroprotective effect; oxidants; Oxidative Stress - drug effects; pathogenesis; peptides; Peptides - chemistry; Peptides - therapeutic use; photoreceptors; retina; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - metabolism; Subcellular localization; vascular endothelial growth factors; Angiogenesis; Crystallins; Minichaperone peptide; Exosomes; Subcellular localization; Apoptosis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2015.05.016

αA- and αB crystallins are principal members of the small heat shock protein family and elicit both a cell protective function and a chaperone function. α-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. 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 α-crystallins in the retina. Prominent expression of αB crystallin in mitochondria may serve to protect cells from oxidative injury. αB crystallin as secretory protein via exosomes can offer neuroprotection to adjacent RPE cells and photoreceptors. The availability of chaperone-containing minipeptides of αB crystallin could prove to be a valuable new tool for therapeutic treatment of retinal disorders. α-Crystallins are expressed in cytosol and mitochondria of RPE cells and are regulated during oxygen-induced retinopathy and during development. α-Crystallins protect RPE from oxidative-and ER stress-induced injury and autophagy. αB-Crystallin is a modulator of angiogenesis and vascular endothelial growth factor. αB Crystallin is secreted via exosomal pathway. Minichaperone peptides derived from αB Crystallin prevent oxidant induced cell death and have therapeutic potential. Overall, this review summarizes several novel properties of α-crystallins and their relevance to maintaining normal retinal function. In particular, the use of α-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. •α-Crystallin is regulated in retinal development and in oxygen-induced retinopathy.•α-Crystallins protect RPE cells from oxidative and ER stress, and autophagy.•αB Crystallin regulates angiogenesis by modulation of VEGF.•αB Crystallin is secreted via exosomes in RPE.•αB crystallin peptides may have therapeutic potential in retinal disease.