Abstract
Presentation Description :
Age related macular degeneration is the leading cause of irreversible vision loss in the western world. Although treatment is available for one form of advanced disease, there remains no means for reducing progression from its early stages. Our work has focussed on the role of the purinergic receptor, P2X7, in age related macular degeneration. In addition to their role as ligand gated ion channels, P2X7 receptors can also act as scavenger receptors. Our work has focussed on examining whether P2X7-mediated scavenger activity is reduced in the early stages of the disease potentially contributing to the development of early signs of the disease . Our work has demonstrated that P2X7 is expressed by a range of neuronal cell types wtihin the retina as well as immune cells including both retinal microglia and blood monocytes. A case-control genetic association study demonstrated increased risk of AMD when single nucleotide polymorphisms of P2X7 and P2X4 receptors are inherited. These single nucleotide polymorphisms are associated with reduced monocyte phagocytosis. Followup structural and functional analysis of P2X7null mice with age revealed an age-dependent increase in features of age related macular degeneration in concert with reduced immune cell phagocytosis. Overall, our studies highlight an important contribution of P2X7 in regulating immune cell function early in the course of the disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.