# Diagnosis and Predictive Value of the Ocular Manifestations of Fabry Disease

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2022 · $515,624

## Abstract

PROJECT SUMMARY
 Lysosomal storage diseases are systemic metabolic disorders caused by pathologic accumulation
of byproducts in various cells and organs, including the eye. Fabry disease is the most common
lysosomal storage disease and results from a mutation of the X-linked GLA gene causing a deficiency
of the enzyme α-galactosidase A (α-Gal A). Glycosphingolipids progressively accumulate, resulting in a
shorter and poorer quality of life from renal failure, cardiac dysfunction, cerebrovascular disease,
gastrointestinal symptoms, and chronic pain. Patients also have pathognomonic cornea verticillata that
is usually present at the time of diagnosis. Other symptoms include cataract, conjunctival and retinal
tortuosity, and aneurysmal dilation. Importantly, a direct correlation exists between the prevalence of
certain ocular findings and disease severity in Fabry disease with cornea verticillata often leading to the
initial diagnosis. The timing of the ocular findings relative to other organ system disease is not well
described and difficult to study in humans because of heterogeneity in the patient population. Mouse
models have been used in the development of enzyme replacement therapy (ERT), but are limited by
the fact that they do not recapitulate ocular phenotypes. Using a Dark Agouti α-Gal A knockout animal
model with the corneal, lenticular, and retinal vascular changes seen in patients, we seek to evaluate
both knockout rats and humans for an ocular pain and retinal phenotypes not previously evaluated in a
in a cohort for this rare disease. Our unique approach integrates the complementary strengths of an
animal model, giving the opportunity to study a large controlled population, while human studies
determine the clinical significance of pathology. We propose to do this with the following specific aims:
1) evaluate the extent and time course of ocular pathology in a α-Gal A KO rat model of Fabry disease
and the effect of early versus later ERT and 2) evaluate human subjects with Fabry Disease for ocular
pain and subclinical ocular changes that precede clinically significant disease observed in α-Gal A KO
rats. This work is expected to have a significant impact on our understanding lysosomal storage
diseases by using an animal model that recapitulates eye symptoms to elucidate the time course of
ocular pathology of Fabry disease in relation to systemic symptoms. These findings will aid in the
determination of optimal timing of ERT initiation and the efficacy of new therapies, while providing
mechanistic insight into the ocular pathology of other lysosomal or metabolic diseases.

## Key facts

- **NIH application ID:** 10376284
- **Project number:** 5R01EY030077-04
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Shyam Sunder Chaurasia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $515,624
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376284

## Citation

> US National Institutes of Health, RePORTER application 10376284, Diagnosis and Predictive Value of the Ocular Manifestations of Fabry Disease (5R01EY030077-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10376284. Licensed CC0.

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