Role of Melanin and a Novel Na:Ca:K Exchanger in AMD

Age-related macular degeneration (AMD) is the leading cause of impaired vision among the elderly in the U.S. Progression of this condition to irreversible blindness is more likely to occur in Caucasians than in Blacks. This finding has led to the suggestion that having more eye pigmentation (melanin) protects against aging changes that cause vision loss in advanced AMD. We propose that a newly discovered protein, called NCKX5, is necessary for pigment synthesis and that impaired functioning of this protein will predispose to the development of advanced AMD. This project will examine the possible role of this novel calcium transport protein in the development of AMD. The activity of NCKX5 in eye cells from Black versus Caucasian donor eyes will be examined. In addition, the project will determine if an experimental animal, the zebrafish mutant golden, which lacks pigment due to mutation of NCKX5, exhibits eye changes like those seen in human AMD. This study will open up new avenues of research into the causes of AMD and will establish whether a powerful animal model, the zebrafish mutant golden, can be used to rapidly and inexpensively test new drugs and clinical protocols to treat AMD.