Good vision requires a clear cornea, which in turn requires a functioning corneal endothelial layer. There are two broad objectives from the proposed research; 1) To characterize the morphologic and functional changes involved in disorders of the human corneal endothelium and 2) to develop a method for permanent corneal storage to improve the overall results of corneal transplantation, the treatment for endothelial failure. We will approach these objectives in three ways, all of which involve the study of human corneal endothelium. First, we will study morphologic and functional changes in the endothelium over long periods in three unique groups of human subjects available to us. A group of 500 consecutive corneal transplants performed between 1976 and 1986 will be asked to return at five year intervals to monitor the response of the endothelial cell layer to the transplanted state. The effects of topical glaucoma medications on the corneal endothelium over five years will be studied in 150 patients recruited for the Ocular Hypertension Treatment Study in which drug and placebo treatment will be randomized. We will study the morphologic and functional effects of aging on the corneal endothelium by repeating specular microscopic and fluorophotometric studies on 61 subjects of various ages first examined 10 years ago. Second, we will study the effects of morphologic changes in endothelial cell on corneal endothelial function in human subjects. Permanent changes are present in diabetics and in contact lens wearers. in addition, markedly enlarged endothelial cells are found in long-term corneal transplants. We will study all three of these conditions with a newly developed method that measures both the rate of corneal recovery from induced swelling and the endothelial permeability to fluorescein, allowing us to estimate both the barrier and pump functions of the endothelial cells. We will also induce corneal acidosis in a group of normal subjects to measure its effect on endothelial permeability and corneal edema. Finally, we will develop a new method for permanent corneal storage involving cryopreservation by vitrification. Vitrification has a number of advantages over conventional colligative methods of cryopreservations. A method for permanent corneal storage will increase the quality of corneal donor tissue by eliminating the time-dependent deterioration that occurs with conventional storage over time. Such a technique will make corneas readily available for emergency use and facilitate tissue matching if its is found to be helpful for certain corneas requiring transplantation.