# Molecular Genetics of a Complement Factor H homolog

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

## Abstract

Project Summary
 Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed
world affecting 11% of adults over the age of 85. In the United States alone, the disease currently
afflicts 10 million individuals with health care costs in the billions of dollars. The 2005 discovery of a
Y402H variant in complement factor H (CFH) as a risk factor for AMD was a major advance in AMD
genetics, however the functional significance of CFH and Y402H in AMD and the pathogenic
mechanisms that initiate the disease process remain poorly understood.
 This proposal will investigate a functional and structural CFH homolog in C. elegans, nematode
complement factor H (nCFH). Although the prevailing hypothesis is that CFH mutations result in
ectopic activation of the alternate complement pathway in the retina, preliminary studies indicate nCFH
assembles on the ciliated dendritic tips of C. elegans mechanosensory neurons where it has a role in
maintaining proximal cilia compartment structural integrity. Additional preliminary data indicate that
cilia compartment structural integrity is compromised in CFH-/- mouse and human Y402H
photoreceptors, indicating that this novel function for nCFH is conserved in its vertebrate CFH
homologs. On the basis of this data, the PI proposes the radical hypothesis that CFH is an essential
structural component of sensory neurons cilia in the vertebrate retina and that defects in sensory
neuron cilia promote AMD pathogenesis in patients with CFH loss-of-function mutations. The aims of
this proposal will extend these preliminary studies and will determine 1) the structural and functional
consequences associated with nCFH partial and complete loss-of-function mutations and 2) identify
cilia, cell surface, and extracellular components necessary for nCFH assembly and function.
Together, the proposed work will provide substantial insight into non-canonical functions of CFH that
are likely to contribute to a novel mechanism of AMD pathogenesis.
!

## Key facts

- **NIH application ID:** 9961611
- **Project number:** 5R21EY030188-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** BRUCE E VOGEL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961611

## Citation

> US National Institutes of Health, RePORTER application 9961611, Molecular Genetics of a Complement Factor H homolog (5R21EY030188-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9961611. Licensed CC0.

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