Crystallins in the retinal neovascularization

Abstract

Abstract: : Purpose: Crystallins are known as proteins mainly existed in the lens. It is reported that alpha–crystallins are expressed in many nonlens tissues and act as small heat shock proteins. On the other hand, while the beta or gamma–crystallins are present in nonlens tissues, their functions are unclear. Our purpose is to explore the functions of crystallins in the retinal neovascularization . Methods: C57BL/6J neonatal mice were exposed to 75% oxygen from the postnatal day 7 to 12 and then returned to the room air. Control mice were kept in the room air. At postnatal day 15, on which oxygen induced retinal neovascularization occurs, eyes were enucleated from the control mice and mice suffered from oxygen–induced retinopathy. mRNAs extracted from the retinas were labeled and hybridized with probes. Microarray analysis was carried out using cRNA probes on Affimetrix MGU74A chips. Fibrovascular tissues from patients with proliferative diabetic retinopathy were used to determine the expressions of crystallins with immunohistochemical study. Results: The microarray showed that growth factors, transcription factors, stress induced proteins, cell markers, and extracellular matrix proteins were up–regulated two folds more than those of the control. These results are in agreement with previous reports for this mouse model. In addition, the crystallin family genes were up–regulated in the group exposed to oxygen. In fibrovascular tissues from diabetic patient, crystallins were expressed around the neovascular vessels. These crystallins were expressed only in glial cells. Conclusions: Crystallin expressions were shown in mouse model of oxygen–induced retinopathy, and in human fibrovascular tissue from proliferative diabetic retinopathy. Our findings suggested that extralenticular expression of crystallins plays a role in the development of retinal neovascularization.

Keywords: crystallins • diabetic retinopathy • retinal neovascularization