Proliferative vitreoretinopathy (PVR) is the most important cause of failure after initial surgical repair of retinal detachments. Although several treatment strategies have been proposed, progress has been limited by our inability to identify those eyes at highest risk, since only 10% of eyes with retinal detachment develop the severe sequelae of PVR. Identification of eyes at highest risk would identify a group of patients who would benefit from new experimental therapies. The goal of this project is to develop a method for predicting which eyes are at high risk for the development of recurrent retinal detachment from PVR, when evaluated at the time of initial surgery or postoperative gas/fluid exchange. We hypothesize that the vitreous fluid/gel forms a microenviromnent that will reflect, if not mediate, the growth and differentiation of PVR-inducing cells along the surface of the retina. Therefore, we predict that analysis of the vitreous for """"""""proliferative activity"""""""" will identify eyes that are desfined to develop PVR from those that will remain quiescent. Specifically, """"""""proliferative activity"""""""" will be characterized by identification of proliferating cells within the vitreous, or alternatively, proliferation-inducing soluble gowth factors. In the first aim, we will utilize animal models for retinal detachment to refine methodology that utilizes flow cytometric techniques to evaluate vitreous-infiltrating cells for proliferation and bioassays for the """"""""net"""""""" stimulatory activity induced by soluble growth factors. In the second and third aims, application of his technology to human vitreous and subretinal fluid samples, respectively, will be evaluated. Finally, in the fourth aim, we intend to initiate a prospective study to evaluate the capacity of these assays to predict the risk of retinal detachment in individual patients.
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