Understanding the Role of Support Cells, Known as Glia, in Geographic Atrophy

This proposal will take a novel approach to studying the pathology of geographic atrophy by investigating the role of glial cells. These cells, traditionally considered only support cells, are altered in geographic atrophy and create a membrane-like structure. The proposed studies will investigate how changes to these cells may influence disease progression and the effectiveness of treatments.

Age-related macular degeneration (AMD) is a leading cause of blindness in people over 60 in the developed world. One area that is severely lacking in our knowledge of AMD is the involvement of cells known as glia, which support retinal function. I have recently observed glial cells exiting the retina and creating a membrane-like structure below the retina in the area where degeneration is occurring in eyes with geographic atrophy, the advanced dry form of AMD. I have also observed these glial cells losing their normal their structure within the retina, which could indicate that they are not functioning normally. The overall goal of my project is to determine the consequences of glial cell changes on disease progression and treatment in geographic atrophy. In the first part of this study, we will investigate whether glial cells below the retina create a barrier. A barrier could protect the retina from toxic factors below the retina but could also prevent the flow of treatments. We will then compare glial cell protein expression in diseased areas to those in normal areas of the retina.

This analysis will tell us whether glial cells are maintaining their normal function in AMD. For this study, we will use human eyes as well as a rat model for geographic atrophy. Our research demonstrates that glial cells touch retinal pigment epithelial cells at the border between normal and diseased areas of AMD eyes. These cells do not make contact with normal eyes. Interestingly, the pathology expands at this border. Therefore, these studies will determine whether glial cell changes contribute to or reduce pathology in AMD. In the second part of this study, we will use cell culture to study how glial cells influence retinal pigment epithelial cells. We will also investigate whether glial cells use small particles, known as extracellular vesicles, to communicate with retinal pigment epithelial cells. This project uniquely examines how changes in glial cells can contribute to disease progression or alter treatment efficacy in AMD. By looking at changes to the glial protein expression, we can understand how these cells can affect other retinal cells. This project will determine whether glial cells are contributing to disease progression in AMD. If glial cell changes are causing detrimental effects, these cells may be potential targets for treating AMD. Such an observation would provide novel therapeutic ideas.