The overall objective of this project is to continue the studies on the physiology, pathophysiology, biochemistry and morphological changes associated with corneal collagenase production. We intend to study the inter-relationships of the corneal fibroblast and corneal stromal inflammation, with the production of enzymes capable of destroying the cornea. The stimulatory effect of corticosteroids on the collagenase system will be examined, as will the best method of inhibiting this effect. The proteolytic enzymes associated with bacterial and viral infections and ulcerations of the cornea will be examined in detail. Finally, an enzyme originating in the granulocyte which is important in facilitating collagenase to degrade tissue collagen, will be isolated and characterized. When the formation from these studies are consolidated, it is hoped that they will provide a more complete understanding of the development of corneal ulcers, the inherent defense mechanisms, and point to the most effective inhibitors of the enzyme system. These will be tested and used in our ongoing studies of proteolytic enzyme inhibitors in the treatment of corneal ulcers.