Interaction of alphaA-crystallin with beta-amyloid in diabetic retina: an emerging antifibrillogenesis activity.

Alpha-Crystallins, the small heat-shock proteins, play a role in protein homeostasis by inhibiting protein aggregation through their ATP-independent chaperone activity. Recently, particular attention has been paid to their role in preventing amyloid fibril formation, suggesting an important implication of these chaperones in amyloid-associated diseases, such as Alzheimer disease and diabetes. Although ?-crystallins are highly expressed in the retina and other ocular structures, and they have been involved in diabetic retinopathy [1], little is known about their potential interaction with amyloid-? (A?) peptides, with special regard to ?A-crystallin (?A-cry). Using retinas from streptozotocin-induced diabetic Wistar rats, we investigated the expression profiles of ?A-cry, A? and their interaction at 2, 4 and 20 weeks after the onset of diabetes, throughout 2D western blot analysis. In diabetic retinas, we detected that both number and intensity of ?A-cry isoforms were increased within 4 weeks and decreased at 20 weeks of diabetes. These changes were inversely correlated with the progressive enhancement in the expression of A?-peptides. In co-immunoprecipitation experiments using retinal extracts at 4 weeks, we assessed a strong interaction of A? with two acetylated ?A-cry isoforms. Therefore, ?A-cry isoforms and A? peptides show an inverse trend of changes over the development of diabetic retinopathy, however, the acetylation of ?A-cry that may positively influence its chaperone activity appear to result in a high binding of A? at the earliest stage of the disease. We propose that ?A-cry/A? interaction may subserve as an initial defensive mechanism to early prevent A? fibrillogenesis and delay retinal degeneration. [1] Kannan R., Sreekumar PG, Hinton DR. Novel roles for ?-crystallins in retinal function and disease. Prog Retin Eye Res. 2012 Nov;31(6):576-604. doi: 10.1016/j.preteyeres.2012.06.001