The goal of this research effort is to better define the pathologic mechanisms involved in a variety of intraocular prolierative disorders, and develop new approaches to therapy. Our approach to this problem consists of three steps: 1) Initially a wide variety of pharmacologic agents including antimetabolies protaglandin inhibitors, and steroids, are tested for their ability to inhibit cellular proliferation in virtro, utilizing cell culture techniques. 2) Promising agents are then evaluated for ocular toxicity following direct intravitreal injection by a combination of clinical, electrophysiologic anh histologic examination. 3) Those agents with most favorable therapeutic indices, including efficacy at low doses in cell culture, and tolerance at high doses following intravitreal injection, and then tested on animal models of intraocular proliferative disorders. Our primary research model involves the intravitreal injection of heterologous dermal fibroblasts in rabbits. This results in both progressive traction retinal detachment similar to MPP in humans, and intraocular neovascularization. This approach has great promise in helping to select potentially useful pharmacologic agents in the treatment of a variety of intraocular prolifeactive disorders in humans.
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