June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Electrophysiological and morphological changes in a low dose sodium iodate induced RPE damage model
Author Affiliations & Notes
  • Nan Zhang
    ophthalmology, Emory University, Atlanta, Georgia, United States
    ophthalmology, Second Xiangya Hospital, Changsha, Hunan, China
  • Xian Zhang
    ophthalmology, Emory University, Atlanta, Georgia, United States
    ophthalmology, Second Xiangya Hospital, Changsha, Hunan, China
  • Preston Girardot
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Vivian Summers
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Micah A Chrenek
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jana T Sellers
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Ying Li
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Salma Ferdous
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Yong-Kyu Kim
    ophthalmology, Emory University, Atlanta, Georgia, United States
    ophthalmology, Hallym University Medical Center, Yeongdeongpo-gu, Seoul, Korea (the Republic of)
  • Debresha Shelton
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • John M Nickerson
    ophthalmology, Emory University, Atlanta, Georgia, United States
  • Jeffrey H Boatright
    ophthalmology, Emory University, Atlanta, Georgia, United States
    Center of Excellence, Atlanta VA Medical Center, Decatur, Georgia, United States
  • Footnotes
    Commercial Relationships   Nan Zhang, None; Xian Zhang, None; Preston Girardot, None; Vivian Summers, None; Micah Chrenek, None; Jana Sellers, None; Ying Li, None; Salma Ferdous, None; Yong-Kyu Kim, None; Debresha Shelton, None; John Nickerson, None; Jeffrey Boatright, None
  • Footnotes
    Support  The studies were funded by the Abraham J. and Phyllis Katz Foundation (JHB); The joint training program between Emory University School of Medicine and Xiangya School of Medicine, Central South University. China Scholarship Council (201806370277 XZ); NIH R01EY028859 (JHB); NIH R01EY021592 (JMN); NIH R01EY028450 (JMN); VA I01RX002806 (JHB); VA I21RX001924 (JHB); VARR&D C9246C (Atlanta VAMC); NIH P30EY06360 (Emory); and an unrestricted departmental award from Research to Prevent Blindness. Inc. to the Ophthalmology Department at Emory University.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2954. doi:
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    • Get Citation

      Nan Zhang, Xian Zhang, Preston Girardot, Vivian Summers, Micah A Chrenek, Jana T Sellers, Ying Li, Salma Ferdous, Yong-Kyu Kim, Debresha Shelton, John M Nickerson, Jeffrey H Boatright; Electrophysiological and morphological changes in a low dose sodium iodate induced RPE damage model. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2954.

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

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Abstract

Purpose : Sodium iodate (NaIO3) is selectively toxic to retinal pigment epithelium (RPE), inducing RPE cell death and subsequent photoreceptor degeneration. We explored differences in NaIO3-elicited responses of RPE and other retinal cells associated with mouse strains and dosing regimens.

Methods : A single dose of NaIO3 at 15 mg/kg was injected intravenously into adult male C57BL/6J and 129/SV-E mice while control animals were injected with the vehicle (PBS). Morphological and functional changes were characterized by fundus imaging, spectral domain optical coherence tomography (SD-OCT), ERG, histological, and immunofluorescence techniques.

Results : The 15 mg/kg NaIO3 dose initially induced a transient increase in scotopic ERG a- ,b-wave and c-wave amplitudes in 12 hours post-injection, followed by progressive structural and functional degradation at 3 days in C57BL/6J and at 1 week in 129/SV-E mice, including depression of ERG response, loss of RPE cells, retinal structure disruption, and thinning of retinal thickness. Strain-difference existed in these two strains: 129SV-E mice showed slower photoreceptor degeneration (7 days post-injection) compared with C57BL/6J mice (3 days post-injection), which indicated that C57BL/6J mice are more sensitive to toxicity of NaIO3. Immunofluorescence imaging revealed Müller cell activation following NaIO3 administration. RPE cell death occurred in a large posterior-central lesion, with a ring-like transition zone of highly irregular, abnormally shaped cells that appeared as early as 12 hours after NaIO3 treatment in both strains. RPE cells in the far periphery survived with generally normal morphology.

Conclusions : The morphological and functional effects of NaIO3 on RPE and retina were dependent on timing, dosage, and strain of mouse. Transient rise and fall of ERG response were thoroughly characterized in both strains. Far peripheral RPE cells were much more resistant to damage than central RPE. It may be that peripheral vs central RPE cells have fundamentally different properties, or location-specific factors mediate these differences in resiliency.

This is a 2021 ARVO Annual Meeting abstract.

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