July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Dark rearing does not prevent prodromal rod oxidative stress in vivo in male Pde6brd10 mice
Author Affiliations & Notes
  • Bruce A Berkowitz
    Anatomy/Cell Biol & Ophthal, Wayne State Univ Sch of Med, Detroit, Michigan, United States
  • Robert Podolsky
    Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, United States
  • Ali M Berri
    Anatomy & Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Kristin Dernay
    Anatomy & Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Fatema Shafie-Khorassani
    Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, United States
  • Robin Roberts
    Anatomy & Cell Biology, Wayne State University, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Bruce Berkowitz, None; Robert Podolsky, None; Ali Berri, None; Kristin Dernay, None; Fatema Shafie-Khorassani, None; Robin Roberts, None
  • Footnotes
    Support  National Eye Institute (RO1 EY026584, BAB), NEI Core Grant P30 EY04068, an unrestricted grant from Research to Prevent Blindness (Kresge Eye Institute, BAB), and the Undergraduate Research and Creative Projects Award of Wayne State University’s Undergraduate Research Opportunities Program (KD).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 959. doi:
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    • Get Citation

      Bruce A Berkowitz, Robert Podolsky, Ali M Berri, Kristin Dernay, Fatema Shafie-Khorassani, Robin Roberts; Dark rearing does not prevent prodromal rod oxidative stress in vivo in male Pde6brd10 mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):959.

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

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Abstract

Purpose : In cyclic light reared Pde6brd10 mice, rod cell oxidative stress contributes to the degenerative phenotype. Dark rearing Pde6brd10 mice slows but does not prevent atrophy. This suggests that outer retinal oxidative stress occurs in Pde6brd10 mice independent of light exposure, a hypothesis that has not yet been tested.

Methods : Pde6brd10 and C57Bl/6 [wild type (wt)] mice were dark reared (DR) until postnatal day 23. In subgroups of DR mice, we measured: i) layer-specific excessive free radical production in vivo via QUEnch-assiSTed MRI [QUEST MRI] in which a positive response was defined as 1/T1 values that are both greater-than-normal with a saline injection and significantly reduced with a methylene blue (MB) injection, ii) superoxide production in whole retina ex vivo (lucigenin), and iii) retinal layer spacing and thickness in vivo (optical coherence tomography, MRI).

Results : Male Pde6brd10 mice had a positive QUEST MRI response localized to the inner segment layer in vivo. Female Pde6brd10 mice did not have a positive response at any retinal depth. Male, but not female, Pde6brd10 mice retina exhibited a supernormal production of superoxide. Male and female Pde6brd10 mice had normal retinal thicknesses.

Conclusions : QUEST MRI is a novel and powerful in vivo approach to measure a relevant oxidative stress biomarker within rod subcompartments co-localized with retinal thickness in experimental RP. The present results raise the possibility that mutant PDE6b protein in DR Pde6brd10 mice is a sufficient condition for generating pre-degenerative inner segment oxidative stress. The unexpected sex difference in this process is discussed.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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