April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
The Function Of Müller Glia In Usher Syndrome Pathology
Author Affiliations & Notes
  • Jennifer B. Phillips
    Inst of Neuroscience,
    University of Oregon, Eugene, Oregon
  • Sabrina Toro
    Institute of Neuroscience,
    University of Oregon, Eugene, Oregon
  • Monte Westerfield
    Inst of Neuroscience,
    University of Oregon, Eugene, Oregon
  • Footnotes
    Commercial Relationships  Jennifer B. Phillips, None; Sabrina Toro, None; Monte Westerfield, None
  • Footnotes
    Support  NIH Grants DC010447, DC004186 and HD022486
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2366. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Jennifer B. Phillips, Sabrina Toro, Monte Westerfield; The Function Of Müller Glia In Usher Syndrome Pathology. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2366.

      Download citation file:

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

  • Supplements

Purpose: : Progressive vision loss in Usher syndrome is due to progressive retinal degeneration. Previously, we showed that the Usher type 1C protein, Harmonin, is expressed in zebrafish and murine Müller glia, and that loss of Harmonin from Müller cells in zebrafish results in diminished visual function, impaired synaptic maturation, and progressive photoreceptor cell death. Here, we explore the potential role of Müller glia in maintaining photoreceptor cell integrity, and the extent to which Harmonin and other Usher proteins may contribute to this function.

Methods: : We used antibodies to six zebrafish Usher proteins to perform immunohistochemistry on cryosectioned retinas from wild-type and ush1c mutant zebrafish of various ages. Retinal tissues were co-labeled for Glutamine synthetase or ZO-1 to visualize Müller cells or tight junctions of the outer limiting membrane (OLM), respectively. Images were obtained with a confocal microscope.

Results: : Zebrafish Harmonin is not produced in photoreceptors before 2 weeks post-fertilization, but is present in Müller cells from 3 days post-fertilization (dpf) through adulthood. Thus, visual defects seen in the first two weeks of life in ush1c mutants result from depletion of Harmonin from Müller glia. Harmonin localizes within Müller glia from the inner limiting membrane to the OLM and in glial processes adjacent to the subapical region of photoreceptors. Harmonin also colocalizes with ZO-1 in the OLM of 5dpf retinas. The zebrafish Usher proteins, Usherin, Gpr98, Cip98a, Cip98b, and Clrn1, are all expressed in Müller glia from larval to adult stages, with localization patterns similar to Harmonin. Müller glial localization of Usherin and Gpr98 is unaffected in the ush1c mutant background.

Conclusions: : All zebrafish Usher proteins examined colocalize in Müller cells throughout life, suggesting a sustained functional role for these proteins. Localization of Usherin and Gpr98 in Müller cells does not depend on the scaffold protein Harmonin, but may instead be mediated by Cip98a or Cip98b. In addition to the previously demonstrated requirement of glial expression of Harmonin in synaptic maturation, the presence of this and other Usher proteins at the OLM and in subapical glial processes suggests additional non-cell autonomous roles for these proteins in maintaining photoreceptor function and survival.

Keywords: retinal degenerations: cell biology • Muller cells • cell-cell communication 

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.