# Inflammatory cells of choroid: a therapeutic target in AMD

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $483,881

## Abstract

The cause of geographic atrophy (GA), a progressive dry form of age-related macular
degeneration (AMD), is elusive and there is currently no therapy for this blinding disorder. Our
prior studies have demonstrated that RPE death is accompanied by attenuation of
choriocapillaris (CC). Like other tissues in the aging body, the choroid is undergoing low grade
chronic inflammation, termed inflammaging. This is logical because, in the GA choroid, there is
elevated complement C3a and 5a, as well as advanced glycosylation end products, and C-
reactive protein (CRP). CRP is an acute phase reactant and an active regulator of the innate
immune system that has been suggested by some to be a risk factor for AMD. There are also
two resident inflammatory cells in choroid, mast cells (MCs) and macrophages. We have
previously demonstrated that macrophages are activated in GA and MC numbers and the
number of degranulated MCs are increased in GA choroid.
 Our recent study demonstrated that simply degranulating MCs with slow-released 48/80
(a snake-venom like compound) causes a GA-like phenotype: degeneration of RPE, visual
function decline, and thinning of retina and choroid. In a pilot study, we observed that slow-
released subconjunctival CRP stimulated MC degranulation in rat choroid and RPE
degeneration. In the proposed studies, we investigate the effect of CRP at a physiologically
relevant level on the RPE/Bruchs membrane/CC complex in vitro and in our in vivo rat model.
 The proposed studies will determine if CRP, which is greatly elevated in AMD choroid,
acts directly on RPE or whether its effect is via activation of macrophages and/or mast cells. All
three cells express Fcγ receptors, which are some of CRP binding sites. If MC degranulation is
the cause of RPE degeneration, we will determine if MC granules or exosomes are responsible.
The RPE migration at the border of GA atrophy is presumed to be epithelial to mesenchyme
transition (EMT) but this has not been characterized and the cause of this event is unknown.
We will first determine if this is EMT in human GA and in our rat model. Then we will investigate
in vitro if CRP stimulates EMT directly or if CRP-induced MC degranulation is the cause.
 Our results will provide new opportunities for understanding GA pathology and
determine the role that choroidal CRP plays in GA. Our studies also have the potential of
identifying novel therapies for GA by quiescing MCs or by preventing CRP from binding its
FCγ receptors.

## Key facts

- **NIH application ID:** 10211184
- **Project number:** 2R01EY016151-15
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Malia Michelle Edwards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $483,881
- **Award type:** 2
- **Project period:** 2006-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211184

## Citation

> US National Institutes of Health, RePORTER application 10211184, Inflammatory cells of choroid: a therapeutic target in AMD (2R01EY016151-15). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10211184. Licensed CC0.

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