# Molecular Basis of Complement Defense in Choroidal Endothelial Cells

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2020 · $193,125

## Abstract

ABSTRACT
Age-related macular degeneration (AMD) is a common, complex disease that results in loss of central
vision. Both genetic and environmental factors contribute to AMD risk, and both operate over
advancing age. In advanced AMD (due to either neovascularization or atrophy), loss of photoreceptor
cells, retinal pigment epithelium (RPE), and choriocapillaris endothelial cells are all observed. Data
from a variety of sources have revealed that eyes with early AMD are characterized by loss of
choriocapillaris endothelial cells and increased activation of the membrane attack complex (MAC) of
complement. The abundance of MAC increases by approximately 2-fold during normal aging, and in
eyes with dry AMD, there is an additional ~ 2-fold increase of MAC compared to normal aging.
Moreover, studies in cultured endothelial cells shows that choroidal cells are susceptible to MAC
mediated lysis, and that this damage can be ameliorated pharmacologically.
A better understanding of the molecular basis for MAC-mediated injury and MAC resistance in
choroidal endothelial cells offers potential avenues for both a better understanding of the disease
process as well as suggesting avenues to intervene in early AMD and, perhaps, prevent progression to
end stage disease. Cells defend themselves from bystander complement injury by both fluid phase and
cell surface inhibitors, but it is likely that other mechanisms that are also controlled by genes are
involved in complement defense, including genes involved in regulating dynamic events at the plasma
membrane.
We propose to investigate the pathophysiology of choroidal endothelial cell death due to complement
injury in AMD by screening a small guide RNA library and the CRISPR-Cas9 system to identify genes
with a regulatory role in affecting choroidal endothelial cell death.
Our experiments will lead to a better understanding of this blinding disease and may help to identify
treatments that can be utilized for patients with AMD.

## Key facts

- **NIH application ID:** 9858360
- **Project number:** 5R21EY029838-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Robert Foster Mullins
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858360

## Citation

> US National Institutes of Health, RePORTER application 9858360, Molecular Basis of Complement Defense in Choroidal Endothelial Cells (5R21EY029838-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9858360. Licensed CC0.

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