Immunolocalization of integrins in the human retina.

PURPOSE: Integrins are cell surface proteins that participate in interactions between cells and with extracellular matrix. Binding of integrins to their ligands influences cell activities including proliferation, migration, and differentiation. Expression of integrin subunits from three different subfamilies were examined in human retina. METHODS: Integrins were detected in frozen sections of two human retinas with an avidin-biotin-complex immunohistochemical technique, using nine different monoclonal antibodies specific for alpha 2, alpha 3, alpha 4, alpha 5, alpha 6, alpha v, beta 1, beta 2, and beta 3. One retina was from a patient who had conjunctival squamous cell carcinoma, and the other was from uninvolved regions of an eye with a choroidal melanoma. RESULTS: All integrins tested were detectable in consistent patterns in two retinas. All except alpha 2 and alpha 4 were stained vibrantly in retinal and choroidal vessels. All alpha subunit staining of vessels showed overlap or close proximity to beta 1 staining. In addition to vessels, beta 1 was also present in the internal limiting membrane; alpha 2, alpha 3, alpha 4, alpha 5, and beta 2 were all found throughout much of the neural retina, albeit with distinctive staining patterns. Other than in association with vessels, alpha 6 and alpha v were not detected in neural retina, and beta 3 was only weakly detected in the nerve fiber layer; alpha 4 and beta 2 were expressed in the retinal pigment epithelium; beta 1 and beta 2 were strongly expressed in drusen present in one of the eyes. CONCLUSION: Nine integrin subunits have been found to have unique distributions in adult human retina. An understanding of the distribution in normal retina can serve as a useful contrast to patterns of staining associated with retinal diseases.

Immunolocalization of integrins in proliferative retinal membranes.

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.