Cytoprotective alpha crystallins in the regulation of RPE cell proteostasis

SummaryAlphaB‐Crystallin (αBC) is an ubiquitous protein with dual function as a molecular chaperone to preserve proteostasis and as an anti‐apoptotic agent. We studied the regulatory role of αBC in murine models of oxygen‐induced retinopathy (OIR), laser‐induced choroidal neovascularization (CNV) and subretinal fibrosis (SF). αBC KO attenuated retinal NV in OIR as compared to WT. In the laser model, CNV lesion size was significantly reduced in αBC KO vs. WT mice. VEGF increased 8 fold in WT vs. αBC KO on day 3 and 7 post‐laser and VEGF secretion was lower in αBC KO vs. WT. Increased mono (tetra)‐ubiquitination of VEGF was observed in αBC siRNA RPE. Further, αBC regulated SF in mice. Attenuation of SF after regression of laser‐induced CNV of αBC KO and a decrease in mesenchymal RPE cells as compared to WT was found. αBC was prominently expressed in SF lesions. TGF‐β induced EMT was further enhanced by αBC overexpression but was inhibited by suppression of αBC. Silencing of αBC inhibited RPE cell proliferation, migration, and fibronectin production. αBC overexpression enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, αBC is an attractive therapeutic target for AMD with an advantage in controlling both CNV and SF.
Source: Acta Ophthalmologica - Category: Opthalmology Authors: Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research