Antisense refers to a nucleic acid molecule that is complementary to an expressed mRNA sequence present in an organism. We are evaluating the use of catalytic antisense molecules (ribozymes) to evaluate the function of specific gene expression in the eye. Ribozymes complementary to interphotoreceptor retinoid-binding protein (IRBP) mRNA have been evaluated in vitro and in vivo. We have also evaluated the use of radiation target analysis (RTA) in determining site-specific function of RNA molecules in vitro by irradiating ribozymes and determining remaining activity. We have developed the world's first human fovea cDNA library, using human retinal tissue collected from donors ranging from two to 79 years of age. Sequencing of clones isolated from the library has revealed that up to 58.6 percent of the genes active in the human fovea may be either new members of known gene families or represent unique genes active in the human fovea. Northern analysis some of these clones has revealed multiple types of tissue expression, with a number of messengers expressed in a retinal-region-specific fashion. There is a correlation of some of these expressed genes with specific macular diseases. We are currently evaluating specific clones for their expression in various retinal regions and for their potential role in age-related macular degeneration.
