We have begun an examination of gene expression in the retinal pigment epithelium (RPE). Our goal is to identify genes expressed specifically or preferentially in the RPE. Mutations affecting such genes constitute etiologic candidates for inherited retinal degenerations. Such genes may also provide gene regulatory elements for targeted gene therapy of the RPE. Three strategies are employed: First, we are analyzing abundant RPE proteins by microsequencing. Although several proteins have been identified, all have general roles in many tissues. Second, we have constructed a bovine RPE cDNA library and sequenced several random clones. A cDNA clone, RPE1, has been identified as the bovine homologue of a human cDNA derived from cutaneous malignant melanoma. At both the mRNA and protein levels, RPE1 exhibits RPE-preferred expression. Third, we are attempting to generate subtracted RPE libraries and perform differential screening. However, we have not identified other RPE-specific clones. Finally, we have performed a candidate gene analysis of the transthyretin gene in fundus albipunctatus and ruled out a causal relationship.