Abstract
Purpose: :
Retinitis Pigmentosa (RP) is a neurodegenerative disease that affects photoreceptors and causes blindness in humans. Recently, it has been shown that norgestrel prevents photoreceptor cells from undergoing apoptosis in two distinct models of retinal degeneration: the light damage model and the Pde6b(rd10) model. The main purpose of this study was to assess if other sexual steroids hormones could offer protection to the retina in another model of retinal degeneration: the rd1 mouse. The rd1 mouse, is characterized by a mutation in the gene encoding for the beta subunit of the rod photoreceptor PDE6, resulting in no protein expression, general PDE6 dysfunction and accumulation of cGMP with a rapid rod photoreceptor degeneration followed by a mutation-independent, secondary death of cone photoreceptors.
Methods: :
Animals were treated in accordance to the ARVO statement for the use of animals in ophthalmic and vision research. 5 mg/kg of progesterone were administered orally to rd1 mice at postnatal days 5, 7, 9 an 11. Animals were sacrificed on postnatal day 12. Histological evaluation was performed usin hematoxylin/eosin and avidin staining, as well as in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay.
Results: :
Many of the rd1 photoreceptors at postnatal day 12 displayed oxidative DNA damage and TUNEL positive reactions. Progesterone administration did not decrease oxidative DNA damage but improved cell survival at the periphery of the retina.
Conclusions: :
Further studies are needed to confirm the mechanism of action of progesterone and the role of other sexual steroid hormones in Retinitis Pigmentosa and other retinal degenerations.Acknowledgements
Keywords: retina • retinitis • neuroprotection