# Regulation of Choroidal Neovascularization in Sorsby's Fundus Dystrophy

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $396,250

## Abstract

PROJECT SUMMARY
Sorsby fundus dystrophy (SFD) is a dominantly inherited, degenerative disease of the macula that is
characterized by bilateral loss of central vision as a consequence of choroidal neovascularization (CNV).
Specific mutations in the TIMP-3 gene involving exon 5 or the intron4-exon5 boundary have been shown to
be causative. Early this year, the AMD consortium identified rare coding variants in the TIMP3 gene when
analyzing 16,144 patients and 17,832 controls. In addition, they identified the first genetic association signal
specific to wet AMD near MMP9. The clinical and histopathological similarities between AMD and SFD
and the identification of variants in the matrix metalloproteinase pathway in AMD suggest that similar
downstream effectors might be in play in both conditions. A better understanding of the pathophysiological
mechanisms contributing to the CNV in SFD will provide information that could be potentially useful in
AMD. In comparative studies using TIMP-3 deficient mice, S156CTIMP-3 transgenic mice and in vitro
culture experiments we have determined that TIMP-3 partially inhibits angiogenesis by blocking the binding
of VEGF to VEGR-2. S156C TIMP-3 mutant protein induces angiogenesis via VEGF and bFGF. We have
also shown that the absence of functional TIMP-3 results in an accumulation of hyaluronan that regulates
choroidal vasculature. Based on these results, we hypothesize that TIMP3 is required to control and localize
matrix degradation in the RPE/choroid, and loss of TIMP3 function in this regards leads to an abnormality in
growth factor/angiogenesis factor, increased HA signaling and neovascularization.

## Key facts

- **NIH application ID:** 9900004
- **Project number:** 5R01EY027083-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** BELA ANAND-APTE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900004

## Citation

> US National Institutes of Health, RePORTER application 9900004, Regulation of Choroidal Neovascularization in Sorsby's Fundus Dystrophy (5R01EY027083-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9900004. Licensed CC0.

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