The long-term objectives of this research proposal are to understand the function of D-serine in the rabbit retina and how it modulates the excitability of ganglion and amacrine cells through its actions as the endogenous coagonist of NMDA receptors. D-serine is synthesized and released by Muller cells and astrocytes and represents a new form of glial-neuronal modulation. Electrophysiological methods will be used to evaluate the direct actions of applied D-serine and reductions of endogenous D-serine will be achieved through biochemical/pharmacological methods. It is essential to understand the importance of Dserine in the retina, because NMDA receptors have been implicated in many functions of nervous tissue, including excitoxicity effects mediated through excessive stimulation by glutamate released from ischemic or diseased tissue. In addition, D-serine is presently given in large quantities for therapeutic purposes to psychiatric patients. Because D-serine can cross the blood brain barrier, it undoubtedly can enter the retina. Thus D-serine represents a potential health risk to the retina and knowledge of its actions and regulation in the retina are essential if D-serine becomes approved therapy for patients.
