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.