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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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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.
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).
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).
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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