Abstract
Purpose:
Retinitis Pigmentosa (RP) is a neurodegenerative disease that affects photoreceptors and causes blindness in humans. Recently, our group has demonstrated the neuroprotective effect of progesterone preventing photoreceptor cells from undergoing apoptosis in rd1 mice, an animal model of retinal degeneration (1). Although there have been numerous attempts to determine the means by which progesterone exerts neuroprotective effects particularly in the brain, studies describing the underlying molecular mechanisms are lacking. The main purpose of this study was to confirm that progesterone offers protection to the retina and its effect on glutamate and glutathione (GSH) retinal concentration.
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 at 2 days interval to rd1 mice at different postnatal days (PN). The administration was started at PN5 ending at PN11, PN13, PN15 and PN17. We obtained retinas from control, rd1 and rd1 treated mice at different PN days (PN 11, 13, 15 and 17), and levels of GSH and Glutamate were determinated by HPLC.
Results:
GSH was decreased and Glutamate concentration was increased in rd1 retinas compared to control retinas when the degenerative process becomes detectable. A statistical increase in the GSH level has been observed in the retina of rd1 mice treated at PN15 in comparison with non-treated mice. We have also observed a statistical decrease in free Glutamate levels in retinas of rd1 mice treated at different PN days (PN11, PN15 and PN17) compared to rd1 retinas. There was not any difference in progesterone effect between sexes.
Conclusions:
These results suggest that the effects of progesterone administration may be linked to a decrease in oxidative stress and glutamate concentration in the rd1 mice.
Keywords: 688 retina •
634 oxidation/oxidative or free radical damage •
426 apoptosis/cell death