July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Ocular Vascular Manifestations of Fabry Disease in α-galactosidase A-deficient Rats
Author Affiliations & Notes
  • Iris S Kassem
    Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
    Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • James J Miller
    Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Chris Reid
    Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Nancy M Dahms
    Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Iris Kassem, None; James Miller, None; Chris Reid, None; Nancy Dahms, None
  • Footnotes
    Support  NIH K08EY024645, R21NS095627, R24HL114474, F30DK113641, T32GM080202, P30EY001931
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6053. doi:
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    • Get Citation

      Iris S Kassem, James J Miller, Chris Reid, Nancy M Dahms; Ocular Vascular Manifestations of Fabry Disease in α-galactosidase A-deficient Rats. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6053.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Fabry disease is an X-linked disorder caused by deficiency of lysosomal α-galactosidase A (α-Gal A) activity from mutation of the GLA gene. Cornea verticillata is a specific finding and lens opacities are common. Vascular tortuosity of the conjunctiva or retina is also a common finding. Rarely, there is vascular occlusive disease seen in patients. We previously developed rats with α-Gal A deficiency and determined that there are corneal and lenticular opacities. We seek to determine if this model expresses any of the ocular vascular phenotypes seen in humans.

Methods : The IACUC at the Medical College of Wisconsin reviewed and approved all animal protocols. All animal research was carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals. CRISPR/Cas9 technology was used to generate α-Gal A deficient (Gla KO) Dark Agouti rats. At 14 to 16 months of age, one eye from each of 13 male rats (7 Gla KO, 6 wild type) was examined under anesthesia with isoflurane. Slit lamp photography and fluorescein angiography (FA) were used to determine if there was any vascular tortuosity or other anomalies. For FA, 100mg/kg of AK-FLUOR 10% was injected subcutaneously.

Results : The conjunctiva of male hemizygous Gla KO rats did not demonstrate any increase in tortuosity compared to wild type rats. The fundus also did not exhibit any tortuosity compared to wild type animals. Retinal vascular patterns also showed no difference. There was an average of 11.86 ± 1.35 and 11.83 ± 0.40 vessels radiating off the optic nerve for Gla KO and wild type rats, respectively (p>0.05 t-test). KO and wild type rats also exhibited no difference in major branching of retinal vessels with 3.71 ± 1.11 and 3.16 ± 1.47 additional vessels, respectively (p>0.05 t-test). The fundus of one knockout rat did demonstrate vascular leakage on FA.

Conclusions : The ocular phenotypes observed in Gla KO rats indicate that this rat model recapitulates some but not all of the ocular phenotypes of Fabry disease. The vascular tortuosity phenotype is not observed, but fluorescein leakage in 1 knockout rat does indicate that there still may be retinal vascular pathology.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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