Our major goal is to improve understanding of the means by which peptide hormone systems subserve ocular function in general and visual function in particular. To pursue this goal, we propose to 1) develop the reagents and materials necessary to examine eye tissues for their contents of eight peptidase enzymes: neutral metalloendopeptidase, aminopeptidases A, M, and P, carboxypeptidase N, peptidyldipeptidase A, dipeptidyl aminopeptidase IV and post-proline cleaving enzyme. Each of these target enzymes is known or believed to degrade one or more of the enkephalins, endorphins, tachykinins, kinins, angiotensins and larger hormone, (e.g. insulin) systems. 2) Using the materials developed in 1), we will examine major tissues and fluids of the eye (notably retina, choroid, optic disk, optic nerve, iris, sclera, cornea, lens, ciliary body, vitreous and aqueous for their contents of the target enzymes. 3) We will then examine these tissues by biochemical, immunocytochemical and autoadiographic techniques to determine which cell-types of a given tissue possess one or more target enzymes and how a given target enzyme is disposed on or within its host cell. By so proceeding we should help clarify which peptide hormone systems are present within the eye and where, among the cell-types of the eye, peptide hormones are likely to be formed and inactivated. To our knowledge, the eye is relatively unstudied in terms of peptide hormone systems, yet there is no portion of the central nervous system better understood than is retina in terms of neuronal interconnections and functions. The latter is to say that there may be outstanding opportunities for clarifying how peptide hormones participate in ocular function once it is known which such hormone systems are present in the eye and where they may act. Preliminary results indicate that the synaptic layer of the retina is an unusually rich source of peptidyldipeptidase A, an enzyme capable of facilitating sympathetic and parasympathetic neurotransmission in other tissues. In addition to generating new information on the cell biology of the eye we anticipate that reagents to be developed through our work program will be of near-immediate usefulness to neurophysiologist concerned with facilitation and modulation of retinal neurotransmission.
