A Genetic Model for Age-Related Cone Degeneration

These experiments use a new animal model, zebrafish, to obtain a better understanding of the genetics of age-related photoreceptor loss and to test new potential therapies.

Age-related macular degeneration (AMD) is a progressive disease that causes blindness. This disease affects the retinal pigmented epithelium (RPE) cells and photoreceptor (light-sensitive) cells, resulting in loss of vision. There is currently no cure. The causes are unclear and difficult to determine due to complexities in genetics related to the disorder and the paucity of animal models. We have recently observed that cone photoreceptors degenerate in aging zebrafish carrying a deletion allele for a known gene. This gene encodes a signaling protein that is secreted by the RPE and supports the development of photoreceptors. Together, these data suggest that the heterozygous condition for this deletion may provide a genetic model for age-related photoreceptor degeneration. The long-term goal of this project is to use these zebrafish to obtain a better understanding of age-related photoreceptor loss and to test new therapies. More ambitiously, the project seeks to use this model of the disease to help identify underlying genetic causes of AMD. The Zebrafish model offers tremendous potential for the study of photoreceptor degeneration related to age, as well as mechanisms for cone replacement.