Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice

• Published in: The American journal of pathology Vol. 187; no. 8; pp. 1670 - 1685
• Main Authors: Vessey, Kirstan A, Gu, Ben J, Jobling, Andrew I, Phipps, Joanna A, Greferath, Ursula, Tran, Mai X, Dixon, Michael A, Baird, Paul N, Guymer, Robyn H, Wiley, James S, Fletcher, Erica L
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2017
• Subjects: Pathology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/j.ajpath.2017.04.016

Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruch membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruch membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease.