Proliferative vitroretinopathy (PVR), a wound healing response occurring in the vitreous is the leading cause of failure of retinal reattachment surgery. This proposal has three major areas of investigation, all of which include the use of pharmacologic agents as an adjunct to conventional vitreoretinal surgery either to reduce the incidence of reproliferation and subsequent redetachment of the retina in cases of PVR or to allow an improvement in mechanical vitrectomy techniques by enzymatically producing a separation at the vitreoretinal interface. All areas of investigation will use our refined, more physiologically relevant rabbit model of experimental PVR produced by lensectomy, vitrectomy and intraocular diathermy. This PVR model will also be tested in the pig. Low molecular weight (LMW) heparin, which is used to reduce bleeding associated with normal heparin, when included in the vitrectomy infusate reduced the incidence of retinal detachment by more than 50 %. In this proposal, the use of LMW heparin for treatment of PVR will be optimized with regard to dosage and treatment schedule. LMW heparin will also be evaluated alone in the pig model and in combination with other antiproliferative agents in the rabbit PVR model. Silicone oil is widely used as a vitreous substitute following vitrectomy to provide long term intraocular tamponade. When used in PVR cases, cellular proliferation often occurs in the areas between the silicone oil and the retinal surface leading to recurrent retinal detachment. In this study, three modified (silicone oil soluble) forms of the widely used antiproliferative agent 5-Fluorouracil (5-FU) will be evaluated for efficacy in preventing PVR in our rabbit model. Some eyes will also be treated with a LMW heparin infusate prior to injection of silicone oil. The rate of release of 5-FU from the silicone oil will be determined. Potential toxicity will be monitored by electroretinography (ERG) and histologically. Despite improvements in mechanical vitrectomy techniques, complete removal of the cortical vitreous from the retinal surface is often difficult and failure to do so can lead to reproliferation. Plasmin, an enzyme which is part of the blood coagulation cascade, has been used by us in a rabbit model to enzymatically produce a posterior vitreous detachment (PVD) (separation between the vitreous and retinal surface). Plasmin will now be used in eyes which have retinal breaks or experimental PVR. Presence of a PVD will be determined by scanning and transmission EM. ERGs will be used to detect damage to the retina by the enzyme. Positive results in any of these projects should lead to clinical use of these pharmacologic agents.
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