June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Histological Characterization of Photoreceptor Degeneration in a Mouse Model of Mucopolysaccharidosis Type IIIC
Author Affiliations & Notes
  • Onkar Sawant
    Eversight, Cleveland, Ohio, United States
  • Jill Wood
    Phoenix Nest Inc, Brooklyn, New York, United States
  • Srikanth Singamsetty
    Phoenix Nest Inc, Brooklyn, New York, United States
  • Xuefang Pan
    Sainte-Justine University Hospital Research Center, University of Montreal, Montreal, Quebec, Canada
  • Sujata Rao
    Ophthalmic Research, Cleveland Clinic, Cleveland, Ohio, United States
  • Alexey Pshezhetsky
    Sainte-Justine University Hospital Research Center, University of Montreal, Montreal, Quebec, Canada
    Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Onkar Sawant, None; Jill Wood, Phoenix Nest Inc (E); Srikanth Singamsetty, Phoenix Nest Inc (E); Xuefang Pan, None; Sujata Rao, None; Alexey Pshezhetsky, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1298. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Onkar Sawant, Jill Wood, Srikanth Singamsetty, Xuefang Pan, Sujata Rao, Alexey Pshezhetsky; Histological Characterization of Photoreceptor Degeneration in a Mouse Model of Mucopolysaccharidosis Type IIIC. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1298.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Heparan-α-glucosaminide N-acetyltransferase (HGSNAT) participates in lysosomal degradation of heparan sulfate. Mutations in the gene encoding this enzyme cause mucopolysaccharidosis IIIC (MPS IIIC) or Sanfilippo disease type C. MPS IIIC is a lysosomal storage disease that causes progressive neurodegeneration in children, leading to dementia and death before adulthood. MPS IIIC patients exhibit incidences of non-syndromic retinitis pigmentosa and early signs of night blindness. The goal of this study was to investigate if retinal degeneration can be detected in the mouse model for MPS IIIC using the Hgsnat knockout (KO) approach.

Methods : Heterozygous mice carrying mutation in the Hgsnat were crossed and offspring were sacrificed at 6 months of age. Eyes were collected for cryosectioing and characterized for cone and rod photoreceptors using cone arrestin, S-opsin and rhodopsin antibodies. Outer nuclear layer (ONL) thickness and number of nuclei in the ONL were measured at every 0.4 mm distance starting from the optic nerve (n=7). Retinal whole mount preparations were labelled with S-opsin and M-opsin antibodies to assess cone opsin gradient and density.

Results : Our data suggest that loss of Hgsnat severely affects rod photoreceptors while cone photoreceptors are mainly unaffected at 6 months of age. We observed more than 33% reduction in the ONL thickness and more than 40% reduction in the number of nuclei in the ONL in the Hgsnat KO retinas compared to those of the wild-type controls (P<0.05). Reduction in ONL thickness and number of nuclei indicate rod photoreceptor degeneration. We also observed thinner outer segments in Hgsnat KO retinas indicating reduced levels of rod photo-pigment rhodopsin.

Conclusions : To our knowledge, these are the first reports of retinal degeneration in the animal model of MPS IIIC. Together our findings indicate that retinal manifestations of MPS IIIC are present even before cerebral manifestations. Thus, ophthalmological evaluations could be used as early diagnostic indicators of disease progression as well as end-points for evaluation of future therapies for MPS IIIC patients.

This is a 2020 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×