# Genetics of Fuchs Corneal Dystrophy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $397,093

## Abstract

Fuchs corneal dystrophy (FCD) is a degenerative disorder of the corneal endothelium that
affects nearly 4% of the population above 40 years of age and accounts for the majority of
transplants performed each year in the US. Despite the health and socioeconomic impact of the
disorder, knowledge of the underlying mechanism and genetic load is sparse, with the only
available treatment being corneal transplant surgery. In this grant application, we will extend our
previous clinical and genetic studies to a) expand our understanding of the clinical presentation
and progression of FCD; and b) begin developing in vitro and in vivo models for the underlying
genetic causes of FCD. Our work consists of three specific aims that draw from the strengths of
an interdisciplinary team. First, we will expand our patient collection and quantitatively document
progression in families linked to known FCD loci (including two novel loci uncovered by our
group in the past year). Second, we will take advantage of the knock-in mouse model developed
recently in our laboratory to understand the cellular basis of familial loss of function mutations in
TCF8 in late-onset FCD families. Finally, taking advantage of our unique cohort, which is
enriched for large, multigenerational families, we will identify novel genes for FCD using a
combination of traditional genetics tools and exon capture coupled to next generation re-
sequencing. These three aims represent a balance of valuable clinical and genetic analyses
coupled with functional experiments designed to dissect the molecular components essential to
corneal endothelial biology and understand biochemical and cellular mechanisms underlying the
disease pathology. Completion of these studies will significantly enhance our understanding of
the genetic basis of this common disorder, offer important new insights into its
pathomechanism, and provide critical measures for establishing disease presentation and
progression rates, which will be necessary for patient management and the design of novel
therapeutic paradigms.

## Key facts

- **NIH application ID:** 10133669
- **Project number:** 5R01EY028538-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** John D Gottsch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,093
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133669

## Citation

> US National Institutes of Health, RePORTER application 10133669, Genetics of Fuchs Corneal Dystrophy (5R01EY028538-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10133669. Licensed CC0.

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