June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
The role of IRE1α in photoreceptor homeostasis and retinal degeneration
Author Affiliations & Notes
  • Dawiyat Massoudi
    Departments of Ophthalmology and Anatomy, University of California San Francisco, San Francisco, California, United States
    Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States
  • Yien-Ming Kuo
    Department of Ophthalmology, University of California, San Francisco, California, United States
  • Alina Olivier
    Department of Medicine, University of California San Francisco, San Francisco, California, United States
    Diabetes Center, University of California San Francisco, San Francisco, California, United States
  • Amen Wiqas
    Department of Pathology, University of California San Francisco, San Francisco, California, United States
  • Scott Oakes
    Department of Pathology, Biological Sciences Division, University of Chicago, Chicago, Illinois, United States
  • Feroz Papa
    Department of Medicine, University of California San Francisco, San Francisco, California, United States
    Diabetes Center, University of California San Francisco, San Francisco, California, United States
  • Douglas B Gould
    Departments of Ophthalmology and Anatomy, University of California San Francisco, San Francisco, California, United States
    Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Dawiyat Massoudi, None; Yien-Ming Kuo, None; Alina Olivier, None; Amen Wiqas, None; Scott Oakes, None; Feroz Papa, None; Douglas Gould, None
  • Footnotes
    Support  NIH Grant EY027810
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1284. doi:
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    • Get Citation

      Dawiyat Massoudi, Yien-Ming Kuo, Alina Olivier, Amen Wiqas, Scott Oakes, Feroz Papa, Douglas B Gould; The role of IRE1α in photoreceptor homeostasis and retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1284.

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

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Abstract

Purpose : Evidence suggests that endoplasmic reticulum (ER) stress is involved in retinal degenerative disorders such as retinitis pigmentosa. ER stress triggers a cell response called the Unfolded Protein response (UPR). IRE1α is an ER resident protein that plays a major role in the UPR. The purpose of this study is to assess the role of IRE1α in photoreceptor developmen,t homeostasis and degenerarion.

Methods : We used mice with IRE1α selectively deleted in rods to test the role of IRE1α in photoreceptor development and homeostasis. We assessed retinal thickness longitudinally using Optical Coherence Topography (OCT) and evaluated the retinal function by electroretinography (ERG) as animal where aged.

Results : OCT at 1 and 3 months did not reveal any changes in mice with heterozygous IRE1α deletion compared to their littermate controls. However, at 6 months old, the heterozygous IRE1α mutant mice had approximately 5% and 10% decreases in retinal and ONL thickness, respectively compared to the controls. ERGs at 6 months old also showed decreased scotopic responses while photopic responses were unchanged. Analyses of the homozygous mice are in progress.

Conclusions : These data suggest that IRE1α is dispensable for rod development but appears to be important for maintaining photoreceptor homeostasis in aging retinas. Future work will evaluate whether there are compensatory changes in the other UPR pathways that could explain the lack of retinal phenotype observed during development.

This is a 2020 ARVO Annual Meeting abstract.

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