DESCRIPTION (Verbatim from applicant's abstract): Age-related macular degeneration (AMD) is characterized by the progressive loss of vision in the central visual field attributable to atrophic, exudative and/or hemorrhagic changes in the macula. One of the hallmarks of AMD is the accumulation of extracellular deposits known as drusen between the retinal pigmented epithelium (RPE) and its blood supply, the choriocapillaris. In this project, our working hypothesis is that specific drusen-associated molecules accumulate in the cytoplasm, or along the basal surface, of "compromised" RPE cells in advance of actual drusen formation. One aim of the proposed research, therefore, is to characterize the role of the RPE in drusen biogenesis. Secondly, having confirmed that a number of drusen-associated molecules do, in fact, have local cellular sources in the retina, RPE, and/or choroid, we propose to determine whether any of these local cell types make a significant biosynthetic contribution to drusen. Accordingly, we propose to identify the relevant cell types, and to determine whether any of these drusen-associated molecules are expressed differentially in individuals with drusen or AMD. Differential expression of gene transcripts in target tissues [cells] in the retina, RPE, and choroid will be analyzed quantitatively using an automated fluorogenic detection system based upon the reverse transcriptase-polymerase chain reaction (RT-PCR). In pursuing these studies, we hope to determine whether changes in the expression of one or more of these genes contributes in a significant way to the cascade of degenerative changes that ultimately manifests itself as AMD.