April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Evidence that Huntington’s Disease Affects Retinal Structure and Function
Author Affiliations & Notes
  • Mary A Johnson
    Ophthal and Vis Science, Univ of Maryland Sch of Medicine, Baltimore, MD
  • Harald Gelderblom
    Experimental Neurology, Charite-Universitätsmedizin, Berlin, Germany
  • Klaus Rüther
    Experimental Neurology, Charite-Universitätsmedizin, Berlin, Germany
  • Josef Priller
    Experimental Neurology, Charite-Universitätsmedizin, Berlin, Germany
  • Steven L Bernstein
    Ophthal and Vis Science, Univ of Maryland Sch of Medicine, Baltimore, MD
    Anatomy & Neurobiology, Univ of Maryland Sch of Medicine, Baltimore, MD
  • Footnotes
    Commercial Relationships Mary Johnson, None; Harald Gelderblom, None; Klaus Rüther, None; Josef Priller, None; Steven Bernstein, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1644. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Mary A Johnson, Harald Gelderblom, Klaus Rüther, Josef Priller, Steven L Bernstein; Evidence that Huntington’s Disease Affects Retinal Structure and Function. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1644.

      Download citation file:

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

  • Supplements

Purpose: Huntington’s disease (HD) is a fatal autosomal dominant genetic disease, characterized by progressive neurologic degeneration affecting muscle coordination, cognition and mood/psychiatric health. HD is caused by a trinucleotide expansion repeat mutation in the Huntingtin (HTT) gene. Disease symptoms typically appear between the 2nd and 4th decades of life, based on the extent of the expansion-mutation. Numerous areas in the affected brain contain HTT-inclusion bodies and protein aggregates produced by the mutant HTT protein. While HTT expansion repeat transgenics have been shown to exhibit retinal photoreceptor degeneration, these models were hampered by artificially long expansions that may cause ‘off effects’. We wanted to evaluate retinal function and structure in an HTT model that more closely resembles the human disease.

Methods: Transgenic knock-in Huntington’s rats containing the human HTT gene with a 60-75 expansion repeat were used. Both Wild type (WT) and mutant pairs from the same litters were evaluated, and at different ages. Following at least 12 hours of dark-adaptation, we measured electroretinograms (ERGs) in pairs of HTT rats and their WT littermates, using the ISCEV protocol and an additional paradigm we developed to expose changes in presumed horizontal cell function. This test measured disinhibition of the photopic response when recorded on a dim vs. bright background. Rats were euthanized shortly thereafter and retinas immunostained for HTT, calbindin (stains horizontal cells), Choline acetyl transferase (ChAT) (stains a subset of amacrine cells), and evaluated by confocal microscopy.

Results: No differences were seen in the ERG a- and b-waves of the HTT and normal rats. However, HTT rats showed reduced oscillatory potential amplitudes and disinhibition of the photopic response. Immunohistochemistry showed HTT accumulation in the horizontal cells and suggested a loss of ChAT (+)-amacrine cells.

Conclusions: Huntington’s disease appears to selectively affect retinal interneurons, causing an unusual inner retinal degeneration, the first such described. Since the disinhibition test appears to selectively target horizontal cell function, this test may be a potential biomarker for future treatment studies.

Keywords: 494 degenerations/dystrophies • 510 electroretinography: non-clinical • 546 horizontal cells  

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.