The transparency of the cornea is dependent upon the intactness and health of the corneal endothelium. Clinically, much corneal disease is seen due to compromised corneal endothelium. The long term objective of this research is to find drugs which will alter corneal endothelial functions in ways that will be beneficial for treating human diseases. Specifically, this research will aim to establish and to characterize, tissue cultures of rabbit, monkey and human corneal endothelium and to develop specific animal models of corneal endothelial degenerations and dystrophies. Non-invasive techniques for assessing corneal endothelial functions in vivo in rabbits and monkeys will be used to correlate the physiological functions of the corneal endothelium with its morphological appearance. This work will provide the basis for considering non-surgical treatment of diseases of this tissue with drugs. The approach emphasizes three components: studies in animal models, studies in tissue culture, from various species, in parallel to the in vivo models, and pharmacological manipulation applied to the physiological and morphological studies of both in vivo and in vitro systems. Parameters measured will include permeability by fluorophotometry, cell density by specular microscopy, corneal thickness by pachymetry, morphological appearance by histology and electron microscopy, mitotic rate by autoradiography and cell counting, and wound closure by planimetry. Model wounds will be created by cryo or physical injury. In the rabbit, an amitotic corneal endothelium will be produced by 5-fluorouracil treatment. Potentially useful pharmacological agents, that will be delivered either topically or intraocularly, and tested for activity, include growth factors and mitogens, steroids, neurotransmitters and their antagonists, attachment factors, cyclic AMP related compounds, prostaglandins and related compounds, ions and chelators, cytoskeleton agents, hyaluronic acid and other biopolymers, and other, new specific agents.
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