Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Rats deficient in α-galactosidase A develop ocular manifestations of Fabry disease. Sci Rep 2019 06 28;9(1):9392

Date

06/30/2019

Pubmed ID

31253878

Pubmed Central ID

PMC6599056

DOI

10.1038/s41598-019-45837-1

Scopus ID

2-s2.0-85068107461   5 Citations

Abstract

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A. Ocular findings, such as cornea verticillata, cataracts, and retinal vascular tortuosity, serve as important diagnostic markers. We aimed to evaluate ocular phenotypes in α-galactosidase A-deficient (Fabry) rats and hypothesized that these rats would manifest ocular signs similar to those observed in patients. Slit lamp biomicroscopy was used to evaluate the cornea and lens, and retinal vasculature was examined by fluorescein angiography in WT and Fabry rats. Mass spectrometry was used to characterize and quantify ocular glycosphingolipids, and histology and electron microscopy revealed the location of the glycosphingolipid storage. We found that Fabry rats developed corneal and lenticular opacities to a statistically greater degree than WT rats. Retinal vascular morphology did not appear grossly different, but there was vascular leakage in at least one Fabry rat. Fabry rat eyes accumulated substrates of α-galactosidase A, and these α-galactosyl glycoconjugates were found in corneal keratocytes, lens fibers, and retinal vascular endothelial cells. Electron-dense lamellar inclusions were observed in keratocytes. Because Fabry rats recapitulate many ocular phenotypes observed in patients, they can be used to study disease pathogenesis and determine whether ocular findings serve as noninvasive indicators of therapeutic efficacy.

Author List

Miller JJ, Aoki K, Reid CA, Tiemeyer M, Dahms NM, Kassem IS

Authors

Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of Wisconsin
Iris S. Kassem MD, PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Genetically Modified
Biomarkers
Corneal Keratocytes
Disease Models, Animal
Eye Diseases
Fabry Disease
Female
Fluorescein Angiography
Male
Rats
Retinal Vessels
Slit Lamp
alpha-Galactosidase