The Inflammatory Cells of the Choroid in Age-Related Macular Degeneration

Imran Bhutto, MD, PhD
Wilmer Eye Institute (Baltimore, MD)
Year Awarded:
2014
Grant Duration:
July 1, 2014 to June 30, 2016
Disease:
Macular Degeneration
Award Amount:
$120,000
Grant Reference ID:
M2014128
Award Type:
Standard
Award Region:
US Northeastern

Co-principal Investigators

Gerard A. Lutty, PhD
Johns Hopkins University/Wilmer Eye Institute

Inflammatory Cells In Choroid During Age-Related Macular Degeneration in Relationship to Retinal Pigmented Epithelium (RPE) Atrophy and Vascular Attenuation

Summary

Macular 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.

Details

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.

About the Researcher

Imran Bhutto is a research associate in the Department of Ophthalmology at the Johns Hopkins University School of Medicine. He completed his doctoral studies in the Department of Ophthalmology at Nagasaki University, Japan, and previously was a postdoctoral fellow in the laboratory of Gerard Lutty, PhD, at Wilmer Eye Institute, Johns Hopkins. Dr. Bhutto is an expert in vascular biology of the retina and choroid and how these vasculatures change in diseases like diabetes and age-related macular degeneration (AMD). His current research focuses on the pathogenesis of AMD and the role of inflammation in AMD. He recently demonstrated that three inhibitors of blood vessel growth were decreased in Bruch’s membrane of AMD subjects, making it susceptible to choroidal neovascularization (CNV). His studies involve aged normal and AMD eyes, as well as animal models of CNV in mouse and rat models. Dr. Bhutto’s goal is to elucidate the cause of AMD so that he might develop therapies to prevent or/and subsequently reduce the morbidity associated with AMD. Prior to receiving this BrightFocus Foundation award, Dr. Bhutto received a grant from the Wilmer Professor Pool fund enabling him to generate preliminary studies that led to the design of experiments to be completed using the BrightFocus Foundation award.