Abstract
Purpose :
Fabry disease is a rare X-linked lysosomal storage disease that affects 1:5000 people. It results from a deficiency of enzyme alpha-galactosidase A and can precipitate cardiovascular, renal, cerebrovascular, and ocular abnormalities, leading to premature death. Prior investigations have suggested a correlation between corneal and lens manifestations and the overall severity of systemic involvement. However, none of these studies have specifically elucidated the relationship between the extent of these symptoms and factors such as age or sex. This investigation evaluated age- and sex- related anterior segment ocular manifestations in a rat model of Fabry disease. We hypothesized that hemizygote male rats will manifest more severe ocular abnormalities as they age compared to heterzygous, wild-type, female, and young rats.
Methods :
A Dark Agouti α-galactosidase A (Gla-m2) rat knock-out model was developed at the Transgenic Core facility of the Medical College of Wisconsin. The animals were stratified into three distinct age cohorts: Group I (8-24 weeks), Group II (25-60 weeks), and Group III (61+ weeks). Intraocular pressure (IOP) was assessed clinically using the iCare TONOLAB tonometer, corneal surface characteristics were examined with a Topcon Slit Lamp Microscope, and corneal thickness (CCT) and anterior chamber depth (ACD) were measured using an Optical Coherence Tomography (OCT) Bioptigen 2200 Imaging Platform. Statistical significance was determined at p<0.05.
Results :
Assessment of ocular features in the Gla-m2 rat model demonstrated significant differences in IOP, tear break-up time, corneal score, CCT, ACD, and lens score dependent on age and sex.
Conclusions :
In summary, the rat model recapitulated ocular manifestations observed in individuals with Fabry disease. Notably, hemizygous male rats were disproportionately affected in all categories, especially in old age. Our comprehensive study suggests the importance in early diagnosis, especially in limiting clinical severity of vision-threatening symptoms. Clinical manifestations, such as cornea verticillata, was present in all cohorts, and Fabry cataracts was evident in hemizygote males and homozygous females.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.