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Maria Miranda, Soledad Benlloch-Navarro, Violeta Sánchez-Vallejo, Laura Trachsel-Moncho, Jose M Soria, Inmaculada Almansa, Javier Araiz; Effect of glutathione ethyl ester, lipoic acid and progesterone on photoreceptor survival in the retina of rd10 mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1733.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis Pigmentosa (RP) is a group of inherited retinal degenerative diseases in which one of several different mutations results in death of photoreceptor cells. Rd10 mice, an animal model of RP, have a missense mutation in exon 13 of the beta subunit of the rod phosphodiesterase (PDE6) gene, its rods express 40% of the endogenous level of the PDE6 protein. In rd10 mice, rod loss starts at post-natal day 18 (P18), peaks at P24 and is almost complete by P35. In previous studies we have shown that GSH is decreased in rd10 retinas just before the degenerative process becomes detectable. Therefore, the purpose of this study was to investigate if three substances (glutathione ethyl ester (GEE), lipoic acid (LA) and progesterone) that have been shown to increase GSH concentrations in other tissues are able to prevent photoreceptor cells from apoptosis in rd10 mice.
Animals were treated in accordance to the ARVO statement for the use of animals in ophthalmic and vision research. Different doses of GEE, LA and progesterone were orally administered to control and rd10 mice at different post-natal days (P15, P17, P19 and P21). Mice were sacrificed at P21. Histological evaluation was performed usin hematoxylin/eosin. Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) and glial fibrillary acidic protein (GFAP) staining were also performed in retinal sections. Retinal GSH concentration was determined by high-performance liquid chromatography (HPLC).
Though GEE, LA and progesterone are able to increase retinal GSH concentration, only progesterone was able to rescue photoreceptors from death, mainly at the periphery of the retina. Interestingly this effect was dose-related, being 150mg/kg the most effective dose in improving cell survival in the retina of rd10 mice. Progesterone was also able to decrease the c gliosis observed in the retina.
We confirm, as we have previously shown in rd1 mice, that progesterone may have a beneficial effect in the delay of photoreceptors death in rd10 mice, though this effect many not only related to its capacity to increase retinal GSH concentrations.
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