# FGF and hyaluronan-mediated alterations in epithelial-mesenchymal transition and metabolism of RPE cells in Sorsby Fundus Dystrophy.

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $621,747

## 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 RPE dystrophy and choroidal
neovascularization (CNV). Specific mutations in the TIMP-3 gene involving exon 5 or the intron4-exon5
boundary have been shown to be causative. The age-related macular degeneration (AMD) consortium has
identified rare coding variants in the TIMP3 gene when analyzing 16,144 patients and 17,832 controls. 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, S179CTIMP-3 transgenic mice and in vitro culture experiments we have determined that RPE cells
expressing mutant TIMP3 undergo epithelial-mesenchymal transformation (EMT) and have altered
metabolism. These changes are correlated with increased bFGF and hyaluronan deposition. Based on these
results, we hypothesize that under physiological conditions, TIMP3 is required to control and localize matrix
degradation in the RPE/choroid which keeps the RPE in an epithelial state and allows for normal metabolic
activity. Loss of TIMP3 function in this regard leads to EMT and altered metabolism which could have
significant effects on RPE and retinal health.

## Key facts

- **NIH application ID:** 10408757
- **Project number:** 5R01EY027083-06
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** BELA ANAND-APTE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $621,747
- **Award type:** 5
- **Project period:** 2017-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408757

## Citation

> US National Institutes of Health, RePORTER application 10408757, FGF and hyaluronan-mediated alterations in epithelial-mesenchymal transition and metabolism of RPE cells in Sorsby Fundus Dystrophy. (5R01EY027083-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408757. Licensed CC0.

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