June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Histological Characterization of Retinal Degeneration in Mucopolysaccharidosis Type IIIC
Author Affiliations & Notes
  • Onkar Sawant
    Eversight, Cleveland, Ohio, United States
  • Jill Wood
    PHOENIX NEST INC, New York, United States
  • Srikanth Singamsetty
    PHOENIX NEST INC, New York, United States
  • Stephanie How
    Eversight, Cleveland, Ohio, United States
  • Xuefang Pan
    Sainte-Justine University Hospital Research Center, Universite de Montreal, Montreal, Quebec, Canada
  • Vera L Bonilha
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Sujata Rao
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Alexey Pshezhetsky
    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); Stephanie How, None; Xuefang Pan, None; Vera Bonilha, None; Sujata Rao, None; Alexey Pshezhetsky, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3237. 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, Stephanie How, Xuefang Pan, Vera L Bonilha, Sujata Rao, Alexey Pshezhetsky; Histological Characterization of Retinal Degeneration in Mucopolysaccharidosis Type IIIC. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3237.

      Download citation file:

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

  • Supplements

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 patients exhibit progressive neurodegeneration, leading to dementia and death before adulthood. Although some MPS IIIC patients exhibit incidences of non-syndromic retinitis pigmentosa and early signs of night blindness, majority of ocular phenotypes are not well characterized. The goal of this study was to investigate retinal degeneration phenotype in the Hgsnat knockout (KO) mouse model and correlate this phenotype with human ocular findings to understand the effects of Hgsnat mutation on the retina.

Methods : Heterozygous mice carrying mutation in the Hgsnat were crossed and offspring were sacrificed at 6 months of age. Cone and rod photoreceptors were analyzed using cone arrestin, S-opsin and rhodopsin antibodies. Outer nuclear layer (ONL) thickness and number of nuclei in the ONL layer were measured. Retinal OCT and fundus imaging was performed on an 11 year old MPS IIIC patient as a routine ophthalmic evaluation. Retinal histology was performed on the eye from 35 year old MPS IIIC donor and compared it to the age-matched control donor-eye.

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 30% reduction in the thickness and number of nuclei in the ONL in the Hgsnat KO retinas compared to those of the controls, indicating rod photoreceptor degeneration (P<0.05). We also observed thinner outer segment length in Hgsnat KO retinas indicating reduced levels of rod photo-pigment rhodopsin. An 11 year old patient showed intraretinal cystic macular edema with myelinated nerve fiber. Severe retinal degeneration was observed in a 35 year old eye-donor.

Conclusions : To our knowledge, these are the first reports characterizing ocular phenotypes arising from deleterious variants in the Hgsnat gene associated with MPS IIIC clinical phenotype. 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 2021 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.