Studies of vitreoretinal vascularized membranes in humans have shown pleomorphism of the new vessels, including transformation to a fenestrated endothelial cell and reduplication of basement membrane and extracellular matrix material. Studies with cultured retinal capillary endothelial cells and pericytes have shown the importance of the extracellular matrix as a determinant of growth. We have previously shown in both rat urethane and rat phototoxic retinopathy that retinal vessels which are incorporated into the pigment epithelial layer alter their morphology from a continuous endothelial cell 9retinal) type to a fenestrated endothelial cell (choroidal) type, with reduplication of basement membrane and new cell synthesis as demonstrated by tritiated thymidine uptake. What is the mechanism for this cellular alteration? In order to test the hypothesis that the structural components of the cells are responsible for this change, we will characterize the biochemical components of the normal basement membrane and cells of the choroidal and retinal capillaries using lectin probes for specific glycoprotein ligands and antibodies to basement membrane components such as collagen, laminin, fibronectin to establish whether there are biochemical differences between the normal retinal and choroidal vasculature. The same probes will be used to characterize the locally altered vessels in urethane and phototoxic retinopathy and in human vitreoretinal vascularized membranes removed at surgery. Similar alterations of endothelial cell morphology have been reported in human diabetic retinopathy and age-related macular degeneration. An understanding of the determinants of abnormal vessel morphology and biochemistry will help understand the influences of the local environment on abnormal vessel growth in disease in vivo. These studies will open an area of investigation in retinal and choroidal diseases - the influence of one cell type in modulating the function and structure of adjacent tissues.
