# The Membrane Attack Complex and the Choriocapillaris in Health and Age-Related Macular Degeneration

> **NIH NIH F30** · UNIVERSITY OF IOWA · 2020 · $36,401

## Abstract

PROJECT SUMMARY
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the western world.
While the etiology of AMD is multifactorial, dysfunction of the choroidal vasculature, which provides the
majority of oxygen to retinal photoreceptors, has been implicated as the earliest detectable event in AMD.
An important contributor to choroidal vascular dysfunction is complement activation. Complement is a
multiprotein component of the innate immune system that results in the formation of a lytic structure known
as the membrane attack complex (MAC). While systemic vascular beds remain free from MAC formation, the
superficial choroidal capillary system known as the choriocapillaris uniquely accumulates the MAC with
advancing age. Such MAC accumulation is proposed to cause lytic injury to choriocapillaris endothelial cells
and the downstream sequelae of AMD. However, the mechanisms that lead to choriocapillaris MAC
accumulation are widely unknown. We hypothesize that unique transcriptional networks drive choriocapillaris
development, which make these endothelial cells particularly susceptible to age-related molecular changes and
MAC-mediated cell death. To test this hypothesis, we propose the following three specific aims:
1. Identify molecular features that make the choriocapillaris uniquely susceptible to MAC formation. We will
differentiate choriocapillaris, arterial, and venous endothelial cells from human induced pluripotent stem cells
and identify transcriptomic drivers of the choriocapillaris cell fate. After single-cell RNA sequencing, we will
functionally validate choriocapillaris-enriched genes that influence MAC formation in vitro.
2. Identify molecular changes in age and AMD that increase choriocapillaris MAC accumulation and MAC-
mediated damage. We will identify choroidal endothelial cell gene expression differences between young, adult
(5th - 6th decade), elderly (8th - 9th decade) and AMD human donors. We will test the degree to which
differentially expressed targets in aging choriocapillaris influence formation of the MAC in vitro.
3. Determine the role of RGCC in response to the MAC in health and AMD. We will quantify RGCC, a gene
recently identified to be highly expressed in human choriocapillaris and implicated in MAC-mediated
endothelial dysfunction, at the RNA and protein level using human choroids from healthy and AMD donors.
We will also functionally assess the degree to which RGCC mediates endothelial cell death and dysfunction in
both choriocapillaris and non-ocular endothelial cell lines.
When successful, these studies will identify novel molecular features that lead to MAC accumulation and
choriocapillaris damage. Further understanding how choriocapillaris cells accumulate and respond to the MAC
may lead to new therapeutic targets for AMD, supporting the Mission, Goals, and Objectives of the NEI.

## Key facts

- **NIH application ID:** 10066428
- **Project number:** 1F30EY031923-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Andrew P Voigt
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $36,401
- **Award type:** 1
- **Project period:** 2020-07-21 → 2024-07-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066428

## Citation

> US National Institutes of Health, RePORTER application 10066428, The Membrane Attack Complex and the Choriocapillaris in Health and Age-Related Macular Degeneration (1F30EY031923-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10066428. Licensed CC0.

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