Inflammatory Cells In Choroid During Age-Related Macular Degeneration in Relationship to Retinal Pigmented Epithelium (RPE) Atrophy and Vascular Attenuation
Co-Principal InvestigatorsGerard A. Lutty, PhD Johns Hopkins University/Wilmer Eye Institute
SummaryMacular degeneration is a progressive eye condition affecting as many as 15 million Americans. The disease attacks the macula of the eye, where our sharpest central vision occurs, affecting reading, driving, identifying faces, watching television, safely navigating stairs, and performing other daily tasks. The retinal pigment epithelium and choriocapillaris, the blood vessels that provide nutrition to the outer retina, die in age-related macular degeneration (AMD). This study will document the inflammatory cells that lie in the choroid of the eye, a layer of blood vessels and connective tissue that lies below the retina, and how they may contribute to this death, if activated. Drugs already exist to control their activation, so this study could suggest new therapies for AMD.
The choriocapillaris (CC) is the only source of oxygen and nutrition for photoreceptors (cells that sense light) and RPE cells (cells that transport molecules between choroid and retina). The CC is severely attenuated in the region of RPE atrophy in geographic atrophy (GA), considered the late stage of dry AMD, and CC death in absence of RPE atrophy, which occurs in wet AMD. Mast cells (MC) are the effector cells of inflammation and immunity. Our preliminary studies suggest that MC degranulation is associated with RPE atrophy and formation of choroid neovascularization (CNV) in AMD. The MC degranulation spills enzymes and cytokines into choroid that could cause RPE and CC death and also cause the thinning of choroid, which is associated with both dry and wet AMD. The goal of this study is to document for the first time the number and activation of the inflammatory cells including MC, microglia (retinal macrophages) and tissue macrophages (TM) in choroid during AMD and determine their relationship to RPE atrophy and vascular attenuation. This is unknown and relevant since inflammation and complement activation have been implicated in AMD previously and the cell types assessed can contribute to a pro-inflammatory environment in choroid. If these cell types investigated in this study are increased in number or activation state in relationship to RPE loss, then this would provide new therapeutic targets in AMD.