Elucidating the Mechanism Behind Altered Retinal Dynamics in Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is among the leading causes of blindness in the western hemisphere, with approximately 30% of people over 60 years old showing symptoms. AMD is characterized by a significant lowering in the zinc concentration in the eye, the formation of dense pockets of highly oxidized lipid particles called drusen in the retinal pigment epithelial (RPE) cells, and altered capability of the RPE cells to regenerate retinal. However, it is unclear how changes in the oxidative state of the lipids and lower zinc concentrations alter rhodopsin photodynamics. The activity of rhodopsin is dependent on the receptor’s lipid environment, with changes in activity occurring with alterations in membrane curvature, thickness, and fluidity. Malfunction of rhodopsin has been linked to multiple eye disorders that cause visual impairment and blindness, including AMD. Much remains unknown about the effect of specific rhodopsin-lipid interactions and how zinc works to stabilize the receptor. To elucidate these effects on rhodopsin stability, we will perform trials to investigate lipid binding and the effects of bulk layer properties on rhodopsin activation. Furthermore, zinc titrations will be performed at varying concentrations to determine how zinc works to stabilize the receptor.