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Maria Miranda, Ramírez-Lamelas Tanya Dolores, Rosa López-Pedrajas, Roberto Gimeno-Hernández, Ángel Fernández-Carbonell, Inmaculada Almansa, Javier Araiz; Combination of oral progesterone and lipoic acid treatment and its effect on oxidative stress in an animal model of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5353. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown the beneficial effects of progesterone (P4) on the evolution of cell death in two animal models of retinitis pigmentosa (RP), the rd1 and the rd10 mice. RP is a complex disease that affects photoreceptors and that have been related to oxidative stress. Indeed, the possible P4 action mechanism may be related to its ability to regulate thiol metabolism and to decrease lipid peroxidation. In an attempt to improve the positive effects of P4, the aim of this study was to combine P4 treatment with a well known and potent antioxidant (lipoic acid (LA)) and to establish the changes induced by this combined treatment in the retina of rd1 mice.
LA (100mg/kg), P4 (100mg/Kg) and a combination of both (LA+P4), were administered orally to rd1 mice at different postnatal (PN) days. On PN11, eyes were enucleated and sectioned (N=6). Histological evaluation was performed using in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Glial fibrillary acidic protein (GFAP) and glutamate cisteyne ligase (GCL) retinal immunohistochemistry were also performed. Additionally, we measured the total antioxidant capacity of LA and P4 and three of their related metabolites (dihydrolipic acid (DHLA), allopregnenolone and estradiol). SPSS software package version 16.0 was used, and the level of significance was set at p<0.05, one-way ANOVA with the corresponding post hoc test was performed.
The combination of P4 and LA administration improved cell survival and showed better photoreceptor protection effect than when administered alone, as shown by the decrease in the number of TUNEL positive cells. In addition, AL, P4 and their combination oral treatment are able to prevent the characteristic gliosis observed in the retina of the rd1 mouse model (74,74% of reduction at the peripheral retina) and a slight decrease of GCLC expression (37,20% of reduction at the peripheral retina) was observed in the retina of rd1 mice treated with the combination of LA and P4 with respect to mice treated only with LA or P4. LA and P4 metabolites have shown higher total antioxidant capacity.
LA and P4 may have neuroprotective actions in the retina and probably their action mechanism is due to their metabolization in the eye.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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