# Muller cell activation and remodeling in AMD.

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $397,094

## Abstract

Age-related macular degeneration (AMD) is a complex, multifactorial disease. I have recently
reported subretinal Müller cell membranes in areas of geographic atrophy (GA). These membranes
closely mimic areas of retinal pigment epithelial cells (RPE) and choriocapillaris loss. I have also
observed Müller cells anterior to drusen expressing glial fibrillary acidic protein (GFAP) and appearing
to migrate to the ONL in eyes with AMD. These data indicate Müller cell activation and remodeling in
AMD. The stimuli for and consequences of these changes, however, are not understood. We
hypothesize that changes to the subretinal milieu in non-neovascular AMD stimulate Müller cell
activation and remodeling that exacerbates AMD pathology.
 The first Aim of this proposal will investigate how Müller cells are affected by subretinal changes that
occur in AMD. We will investigate Müller cell morphological and metabolic changes anterior to drusen in
human donor eyes with AMD. We will then evaluate the Müller cell response to drusen components,
amyloid beta and oxidized lipids, in vitro. The second subAim of Aim 1 will determine the effect that
RPE cells exert on Müller cells. While these cells are normally separated by the photoreceptor
segments, subretinal pathology as well as their abnormal migration and extension allows them to touch
in eyes with AMD. We will analyze the RPE influence on Müller cells using human AMD tissue and cell
culture experiments.
 The second proposed Aim focuses on how Müller cells in the subretinal space affect neighboring
cells. We will first investigate how Müller cells affect RPE cells using cell culture experiments. We will
also investigate extracellular vesicle release by Müller cells and, if present, determine what effect these
have on RPE cells. We will also investigate the composition of the subretinal glial membranes that we
have observed in GA. Since it is not possible to determine in human retinas how early in the disease
process glia intrude the subretinal space, we have developed a rat model with focal RPE cell atrophy.
We will also determine whether these glial membranes form a scar which will prevent the flow of
material, including future stem cell therapy, from the retina to subretinal space. Finally, we will inhibit
the membrane and determine how this affects disease progression in our rat model of RPE atrophy.
 These studies will determine the role glia play in AMD pathology, potentially identifying novel
treatments. By investigating extracellular vesicle and exosome release from Müllers, our studies will
identify how Müller cells interact with other cell types in the normal and diseased retina.

## Key facts

- **NIH application ID:** 10330578
- **Project number:** 5R01EY031044-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Malia Michelle Edwards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $397,094
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330578

## Citation

> US National Institutes of Health, RePORTER application 10330578, Muller cell activation and remodeling in AMD. (5R01EY031044-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10330578. Licensed CC0.

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