Identification of Retinal Degeneration Loci: Adhesion and Phagocytosis
Authors:Samuel Bounds, Arash Ghaffari-Rafi, Tiffany Mao, Jackie Mao, Sampat Sindhar, Alex Tonthat
Mentor:Frank Laski, Professor of Molecular, Cell and Developmental Biology, UCLA
Genomic screens provide an exciting avenue for accelerating the discovery of loci contributing to specific diseases, including age-related retinal degeneration (RD), the leading cause of blindness in the United States and worldwide. Via a screen exploiting the model organism Drosophila melanogaster, our study bids to identify new RD loci and their functions. Although past research in D. melanogaster has focused on recessive viable genes, ours examines recessive lethal, which have yet to be studied and are more difficult to study for RD mutant phenotypes—hence requiring nontraditional genetic techniques to identify these genes. We used an RNAi approach, in which double stranded RNA (dsRNA) is expressed only in the D. melanogaster visual system to knockdown the gene of interest. Then these transgenic flies are aged in light and histologically analyzed for any signs of RD. In preliminary experiments, my screen of 130 phagocytosis and cell adhesion genes identified 11 loci with potential RD mutant phenotypes. In particular, expression of dsRNA of the cell membrane protein Amalgam resulted in a severe age-dependent RD. I also report the potential of Amalgam playing a role in light dependent RD, in which proper cell adhesion may be paramount for inhibiting photoreceptor atrophy. This report presents a summary of the newly identified genes contributing to RD susceptibility, and proposes a future course of action for elucidating the non-phototransduction molecular processes contributing to visual impairments.