Retinal pigment epithelial cells have been implicated as a major cell type involved in proliferative vitreoretinopathy and epiretinal membrane formation. Several studies have focused on the occurrence of proliferation of retinal pigment epithelial cells in the vitreous cavity. However, there is very little information concerning how these cells gain access to the vitreous cavity. A likely candidate is cellular migration. There is indirect evidence from several sources that retinal pigment epithelial cells are capable of such migration. Our studies have demonstrated retinal pigment epithelial cell migration in vitro. In addition, an animal model has been developed which suggests that RPE chemotaxis has significance in vivo. We propose to study the basic mechanisms involved in retinal pigment epithelial cell migration. Our ultimate goal is to find a means to inhibit RPE migration, which we feel plays a major role in proliferative vitreoretinopathy and epiretinal membrane formation. Fibronectin and platelet-derived growth factor have been demonstrated to be chemoattractants for RPE cells. Using these and any other chemoattractants which are found, we will examine mechanisms involved in RPE cell migration. Sepcifically, we would like to know if cell surface receptors for chemoattractants can be demonstrated, whether protein carboxymethylation reactions are required for chemotaxis, whether phospholipase A2 plays a role, what intracellular messengers are involved, and what role the cytoarchitecture plays in RPE chemotaxis. We will examine substances known to block the biochemical processes we find to be important for RPE chemotaxis, for their ability to inhibit RPE chemotaxis in vitro. Any agents which are found to inhibit retinal pigment epithelial cell migration in vitro will be examined for their ability to inhibit RPE cellular membrane formation in the animal model of proliferative vitreo-retinopathy mentioned above. Finally, substances which appear to show therapeutic promise will be examined for ocular bioavailability and ocular toxicity.
