July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Norgestrel-treatment does not prevent rod oxidative stress in vivo in dark-reared Pde6brd10 pups
Author Affiliations & Notes
  • Bruce A Berkowitz
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, Michigan, United States
  • Robert H Podolsky
    Beaumont Hospital, Michigan, United States
  • Karen M Lins-Childers
    Beaumont Hospital, Michigan, United States
  • Sarah Roche
    University College Cork, Ireland
  • Thomas G Cotter
    University College Cork, Ireland
  • Robin Roberts
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Bruce Berkowitz, None; Robert Podolsky, None; Karen Lins-Childers, None; Sarah Roche, None; Thomas Cotter, None; Robin Roberts, None
  • Footnotes
    Support  EY026584 (BAB), AG058171 (BAB), EY04068 (OVAS core), an unrestricted grant from Research to Prevent Blindness (Kresge Eye Institute), and Science Foundation Ireland (SFI 13/IA/1783, SR and TC)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4868. doi:https://doi.org/
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    • Get Citation

      Bruce A Berkowitz, Robert H Podolsky, Karen M Lins-Childers, Sarah Roche, Thomas G Cotter, Robin Roberts; Norgestrel-treatment does not prevent rod oxidative stress in vivo in dark-reared Pde6brd10 pups. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4868. doi: https://doi.org/.

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

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Abstract

Purpose : Norgestrel is a synthetic progesterone analogue with anti-oxidant properties (PMC5065647). In 12:12 cyclic light reared Pde6brd10 mice, norgestrel also reduces pro-inflammatory activation of microglia causing a substantial slowing of outer retinal atrophy (PMC5096718). Dark-reared Pde6rd10 mice show outer retinal oxidative stress only in superior retina of males by post-natal day (P) 23 (PMC5868999). Since less is known about dark-reared Pde6rd10 etiology, we test the hypotheses that dark-reared Pde6rd10 pups experience outer retina microglia activation and benefit from norgestrel anti-oxidant properties.

Methods : Dams of P10 Pde6brd10 pups were either untreated or given a Norgestrel-supplemented diet (80mg/kg/day) (PMC5096718). Mice were dark-reared (to remove confounding effects of light and slow degeneration) until P23. Ora serrata-to-ora serrata microglia activation was assessed in untreated Pde6brd10 mice histologically. In treated pups, outer retina excessive free radical production in vivo was measured with QUEnch-assiSTed magnetic resonance imaging (QUEST MRI) (PMC5868999).

Results : Microglia activation and outer nuclear layer thinning were limited to superior retina in untreated male and female P23 Pde6brd10 pups. Norgestrel-treated male P23 male Pde6brd10 mice showed a similar spatial extent of outer retina oxidative stress in vivo in superior retina as previously reported in untreated male pups; norgestrel-fed male P23 female Pde6brd10 mice did not show outer retinal oxidative stress, in agreement with earlier results (PMC5868999).

Conclusions : These findings further highlight superior retina in the pathogenesis of rod atrophy in dark-reared Pde6rd10 pups. The data also suggest that outer retina oxidative stress occurs via a norgestrel-insensitive mechanism.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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