# Inflammatory cells of choroid: a therapeutic target in AMD.

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $513,062

## Abstract

We have documented the loss of choriocapillaris (CC) in all stages of age-related macular
degeneration (AMD) during the past 4 years. In early and intermediate AMD, the previously
undocumented loss of CC was often accompanied by hyperplastic vascular structures or buds that we
presume are the earliest form of choroidal neovascularization (CNV). In geographic atrophy (GA) the
significant CC loss appeared to occur after the retinal pigment epithelium (RPE) have atrophied. In
neovascular AMD, the loss is adjacent to CNV where there is a monolayer of RPE present, so CC
loss precedes RPE loss. We now want to investigate the cause of CC and RPE loss.
 Recent work suggests that inflammation is involved in AMD. We find that choroid is a
proinflammatory milieu, having elevated C-Reactive Protein (CRP), complement components (C3a,
C5a, C5b-9), and advanced glycosylation end products. We recently investigated the inflammatory
cells of choroid: macrophages and mast cells (MCs). There were increased numbers of activated
macrophages (IBA1+/HLA-DR+) in AMD choroid. There were significantly more MCs and more
degranulating MCs in all AMD choroids. Degranulation was often associated with pathological
changes in the CC. These results suggest the following hypothesis: choroidal MC degranulation
results in thinning of choroid, death of RPE and CC, and activation of choroidal macrophages,
events that occur in AMD. In Aim 1, we will use a rat model of choroidal MC degranulation to
determine the effects of MC degranulation on a normal choroid. Aim 2 focuses the effect of MC
degranulation after different stimuli, which are known to be present and elevated in AMD choroid, on
RPE and choroidal endothelial cell (CC EC) viability and formation of a monolayer in vitro. MC
quiescence has been the focus of pharmaceutical companies for years so we hypothesize that MC
degranulation is a druggable target and quiescing and stabilizing MCs can curtail progression
of the AMD phenotype in our rat model. To address this hypothesis, we will focus in Aim 3 on FDA
approved topical drugs (Chromolysin, Ketofilin fumarate) and determine if topical or oral
administration prevent choroidal MC degranulation in our rat model and prevent induction of AMD like
changes in choroid. Finally, in Aim 4, we will characterize the choroidal MCs in AMD versus aged
controls and assess the choroidal milieu in clinically documented human AMD versus aged control
subjects without AMD to elucidate new targets for therapy to prevent degranulation.
 The proposed studies have the potential to elaborate the role of choroidal MCs in AMD and
potentially demonstrate that generic FDA-approved drugs could be repurposed to control MC
degranulation and allay progression of AMD.

## Key facts

- **NIH application ID:** 9928925
- **Project number:** 5R01EY016151-14
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Malia Michelle Edwards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $513,062
- **Award type:** 5
- **Project period:** 2006-09-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928925

## Citation

> US National Institutes of Health, RePORTER application 9928925, Inflammatory cells of choroid: a therapeutic target in AMD. (5R01EY016151-14). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/9928925. Licensed CC0.

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