June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Multimodal imaging in patients with MYO7A-related Usher syndrome
Author Affiliations & Notes
  • Leslie Small
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
  • Jessica Wong
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
  • Mark E Pennesi
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Hao Zhou
    Bioengineering, University of Washington, Seattle, Washington, United States
  • Ruikang K Wang
    Bioengineering, University of Washington, Seattle, Washington, United States
  • Abhishek Chadha
    Stein Eye Institute, University of California, Los Angeles, Los Angeles, California, United States
  • David S Williams
    Stein Eye Institute, University of California, Los Angeles, Los Angeles, California, United States
  • Austin Roorda
    School of Optometry and Vision Science, University of California, Berkeley, Berkeley, California, United States
  • Travis Proco
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
    Francis I Proctor Foundation, Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
  • Jacque L Duncan
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Leslie Small, None; Jessica Wong, None; Mark Pennesi, None; Hao Zhou, None; Ruikang Wang, None; Abhishek Chadha, None; David Williams, None; Austin Roorda, Light Technologies (C), University of California, Berkeley (P), University of Rochester, University of Houston (P); Travis Proco, None; Jacque Duncan, 4D Therapeutics (C), Acucela (F), AGTC (C), Allergan (F), Biogen/Nightstar (F), Biogen/Nightstar Therapeutics (C), Editas Medicine (C), Eloxx (C), Foundation Fighting Blindness (C), Neurotech (F), ProQR Therapeutics (C), Second Sight Medical Products (F), SparingVision (C), Spark Therapeutics (C), Vedere Bio (C)
  • Footnotes
    Support  Foundation Fighting Blindness, Research to Prevent Blindness, NEI R01-EY023591 and NEI U24EY029891 and NEI U24EY029891.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 228. doi:
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    • Get Citation

      Leslie Small, Jessica Wong, Mark E Pennesi, Hao Zhou, Ruikang K Wang, Abhishek Chadha, David S Williams, Austin Roorda, Travis Proco, Jacque L Duncan; Multimodal imaging in patients with MYO7A-related Usher syndrome. Invest. Ophthalmol. Vis. Sci. 2020;61(7):228.

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

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Abstract

Purpose : Usher syndrome type1B (USH1B) is associated with variants in the MYO7A gene, which is expressed in retinal pigment epithelium (RPE) and photoreceptor (PR) cells. Most information about cell survival has come from imaging affected patients because mice with MYO7A variants do not develop photoreceptor degeneration. We characterized RPE and PR structure in eyes with USH1B with high-resolution retinal imaging modalities.

Methods : Confocal and non-confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) were used to observe the cone PR mosaic in this cross-sectional study of patients with variants in MYO7A. Regions of interest (ROI) were selected at 1 degree intervals in the central 5° where mosaics of at least 50 cones were seen. Cone spacing was calculated as the average nearest neighbor distance using a density recovery profile analysis, and converted to Z-scores (standard deviations from the mean) to account for changes in cone spacing with eccentricity from the fovea. Fibroblasts were isolated from a skin biopsy from the oldest patient and converted to induced pluripotent stem cells (iPSC), then differentiated to RPE cells to study RPE morphology in cell culture.

Results : 4 USH1B patients (4 eyes) ranged in age from 8-37 (mean 19+14) years, with duration of visual symptoms ranging from 5-27 (mean 11+11) years. AOSLO imaging showed cone mosaics in 3 of the subjects; the oldest subject had severe PR degeneration and cystoid macular edema. All patients imaged with AOSLO had ROI with cone spacing Z-scores greater than 2, but the fraction of ROIs with normal cone spacing was large (over 84% in all cases). iPSC cultures differentiated into well-polarized RPE cells, forming an epithelial-like “cobblestone” appearance. Western blot data showed no evidence of myosin-7a protein, and the cultures were found to be amenable to mutant phenotype analysis (described elsewhere).

Conclusions : In eyes with USH1B, PR were well-preserved in the macula with increased cone spacing in a fraction of regions. Since ROIs were selected at locations where measurable cones were visible, the results are a best-estimate of retinal health. Multimodal imaging of patients with USH1B demonstrates the importance of MYO7A in PR and RPE cell structure. Investigations of iPSC-RPE cell cultures, derived from USH1B patients, are expected to provide further insight into the pathogenesis of USH1B-retinal degeneration.

This is a 2020 ARVO Annual Meeting abstract.

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