The major objective of this research project is to determine basic mechanisms of experimental ocular inflammation, particularly those changes occurring in blood vessels and how they affect the inflammatory process. A particular stress will be the effect of intravascular coagulation and cell-mediated immune mechanisms on the pathogenesis of ocular vascular permeability. The project is in four parts. 1) The effect of coagulation mechanisms on ocular immune inflammation will be studied in a model of cell-mediated immunity in the guinea pig eye with and without anticoagulation and by super-imposing an unrelated intravascular clotting episode on various forms of experimental uveitis, primarily in the rabbit. 2) A study will be made of the cell populations, particularly lymphocytes, and mononuclear phagocytes, participating in altered ocular, vascular permeability following intracorneal and intravenous bacterial endotoxin (lipopolysaccharide). Systemic effects will be analyzed in a mouse model using specific cell transfers from strains sensitive to and strains resistant to the effects of endotoxin. 3) The capacity of a) circulating endotoxin and b) concurrent cell-mediated immunity to localize immune complexes in the rabbit eye will be studied. The effect of intravenous immunogen challenge on ocular vascular permeability will also be examined following adoptive transfer of specific cells. 4) The effect of acute and chronic intravascular coagulation on experimental diabetic retinopathy will be studied in rats treated with streptozotocin. Alterations in vascular permeability will be quantitated in all these studies with albumin and fibrinogen labeled with 125 and 131-Iodine. Endothelial cell proliferation will be assessed in selected studies by the incorporation of tritiated thymidine and histopathologic studies will include fluoroescence and electron microscopy when necessary.
