Immunolocalization of integrins in proliferative retinal membranes

Abstract

Purpose: Integrins are cell surface adhesion molecules that serve as receptors for extracellular matrix components or for other cells. Integrins help regulate processes such as cell proliferation, migration, and differentiation. These processes are thought to have fundamental roles in the pathogenesis of proliferative retinal membranes in diseases such as proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Therefore, the authors sought to determine the expression pattern of integrins in human proliferative membranes.

Methods: Tissue was obtained from two patients with PVR, two with PDR, and one subretinal neovascular membrane from a patient with presumed ocular histoplasmosis. Integrins were detected with an avidin-biotin-complex immunohistochemical technique using nine different monoclonal antibodies specific for alpha subunits 2, 3, 4, 5, 6, and V, and beta subunits 1, 2, and 3.

Results: All integrin subunits studied were detectable to varying degrees in proliferative membranes. beta 1 and alpha 6 were especially prominent at the edges of most PVR and PDR membranes. Pigmented cells expressed up to nine different integrin subunits, in contrast to normal RPE cells, which immunostained for only alpha 4 and beta 2. Proliferative diabetic retinopathy vessels expressed all nine integrin subunits examined, including alpha 4, which was poorly expressed in vessels of nondiabetic retinas.

Conclusions: Integrin subunits are readily detectable in pathologic membranes. Both PVR and PDR are associated with altered integrin expression in vascular endothelium and pigmented cells. The distribution of integrins at the edge of a membrane suggests a role in the growth or contraction of the membrane, presumably by participating in the interaction between cells and substances such as vitreous collagen. Therefore, integrin antagonists may hold promise for the treatment of proliferative retinopathies.