The objective is to study the pathogenesis of corneal edema which can occur from disease (i.e., endothelial dystrophies, contact lens wear, diabetes, inflammation) and which occurs following intraocular surgery. Clinically following cataract, vitrectomy and anterior segment surgery, an increase in corneal thickness and loss of endothelial cells occurs, which reflects both a compromised barrier and pump function. A cornea that has presurgical polymegathism appears to also have a greater predisposition toward corneal edema following intraocular surgery, and this is especially true for the diabetic patient, a patient with guttate and may be the case for long term contact lens wearers, all of whom have severe endothelial polymegathism, and are at the age for cataract surgery. The proposed studies should further our understanding of the pathogenesis of corneal edema and the prevention of post-surgical corneal edema. Answers will be sought to the following specific aims: (1) Is polymegathism related to corneal endothelial cytoskeleton change? The corneal endothelium of contact lens wearers, diabetic, age related polymegathism and following wound healing will be studied. Comparison of endothelial volume regulation changes (hrs) will be compared to endothelial cells changes that occur over months and years. The cytoskeleton changes will be measured by NBD-phalloidin staining of the F-actin and quantified by measuring the total F-actin by a DNase I and phalloidin binding assay. (2) The effect of 12(R)HETE which is formed by the corneal epithelium via P450 metabolism of arachidonic acid will be evaluated for its role in altering the endothelial cytoskeleton, pump and barrier function. The diffusion of 12(R)HETE across the cornea, its metabolism and breakdown products will be determined for their role in changing the endothelial metabolic pump function. (3) Is polymegathism associated with alterations in corneal endothelial metabolism as measured by QO2, glucose metabolism, ATPase activity, cAMP/cGMP, protein kinase """"""""C"""""""", cytochrome oxidase and mitochondrial NADPH. And (4) what is the effect of endotoxin on the corneal endothelial barrier and pump function? These studies will be performed on in vitro perfused human (obtained from GA Eye Bank) cat (with low cell number), rabbit and rat (normal and diabetic) corneas. The results of these studies should provide a better understanding of the corneal endothelium in post-operative corneal edema and will answer the question if contact lens induced polymegathism will predispose a cornea toward post-operative edema.
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