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Rescue of photoreceptor degeneration by progesterone in an animal model of retinitis pigmentosa
Author(s) -
Miranda M.,
BenllochNavarro S.,
TrachselMoncho L.C.,
Ramírez D.T.,
LópezPedrajas R.,
Almansa I.,
Silvestre D.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0307
Subject(s) - retinitis pigmentosa , lipid peroxidation , oxidative stress , retinal degeneration , endocrinology , malondialdehyde , medicine , glutathione , tunel assay , erg , glutathione peroxidase , chemistry , andrology , biology , retinal , biochemistry , superoxide dismutase , immunohistochemistry , enzyme
Purpose Retinitis Pigmentosa ( RP ) is a neurodegenerative disease, resulting in progressive death of photoreceptors. rd10 mice are a model of RP that have a mutation on the cGMP phosphodiesterase codifying gene. The aim of this study is to evidence the neuroprotective role on photoreceptors of progesterone. Methods Progesterone was orally administered (150 mg/kg at postnatal days 15, 17, 19 and 21). The last day, eyes were enucleated and sectioned or homogenized. Sections were stained with hematoxilyn‐eosin and TUNEL assay was performed. Alterations of different proteins ( pCREB , CREB , BDNF , TNF α and LC 3) were determined by western blot ( WB ). Oxidative stress markers (glutathione ( GSH ) and malondialdehyde ( MDA )) were determined by HPLC . To explore PG mechanism, ARPE ‐19 PG treated cells were exposed to H2O2 and cell viability was measured. Tissue homogenates were also exposed to a biochemical induction of lipid peroxidation, and the effect of PG was studied. Results Hematoxilyn‐eosin and TUNEL assays revealed that histological degeneration decreased with PG . No differences were obesrved in WB analyzed proteins between control and rd10 retinas. Retinal GSH / GSSG ratio was decreased and MDA increased in rd10 mice, and PG restored these alterations. After H 2 O 2 stress, major viability was detected on ARPE ‐19 PG treated cells and inhibiton of lipid peroxidation was observed in tissue when PG was added. Conclusions Results suggest that progesterone protection could be related with its antioxidant ability.