The purpose of this collaborative proposal is to examine the cellular and molecular mechanisms of action of neurotrophic factors in the mammalian retina. In this proposed set of experiments, we are specifically focusing on brain derived neurotrophic factor (BDNF) and its receptor molecules (trkBs). Photoreceptor outer segment degeneration is one of the main cellular events that occurs when the neural retina is separated from the underlying retinal pigment epithelium (retina detachment). In preliminary experiments, we have determined that the administration of BDNF rescues photoreceptors from certain degeneration following detachment and promotes the regrowth of their outer segments in the absence of reattachment to the retinal pigment epithelium. The overall goals of this proposal are to determine the molecular and cellular mechanisms mediating BDNF's effect. The project will use the tools of molecular and cellular biology to accomplish the following specific aims: l) To identify the repertoire of BDNF receptors (isoforms of trkB) expressed in the retina; 2) To determine the expression profile of these trkB isoforms in normal, detached, BDNF treated non-detached retinas, and BDNF treated detached retinas.; and 3) To begin to assess the functional capabilities of the various trkB isoforms. Because retinal detachment, and other conditions in which photoreceptor outer segments degenerate, are a major cause of visual disability, any advancement in knowledge that may result in either a direct therapy or provide mechanisms for the molecular basis of retinal degeneration are of medical significance. Additionally, this project will add significantly to our understanding of the role of this important family of neurotrophins in the development and maintenance of the normal retina.