Rol of Retinoid X Receptors on survival and modulation of inflammatory response in a mouse model of Retinitis Pigmentosa.

TURPAUD AXEL; VOLONTÉ YA; AYALA PEÑA V.B; GARELLI A; ROTSTEIN N.P.; POLITI L.E.; GERMAN O.L.

córdoba

Congreso; XXXIII CONGRESO ANUAL SAN 2018 CORDOBA ? ARGENTINA 24 AL 26 DE OCTUBRE; 2018

Retinal neurodegenerative diseases, which have no effective treatments, share as a final common step the photoreceptor cells (PhR) death. Also inflammation has a role in these pathologies. Retinoid X receptors (RXR) have the capacity of modulate and integrate multiple cell functions; and their activation has shown beneficial clinical effects in animal models of chronic inflammatory diseases. In this work we assessed whether this receptors might prevent PhR death and/or inflammation.Using rd1 mice, we analyze in vivo and in vitro the roles of RXR in retina degeneration. Here, we show, by qRT-PCR analysis, that the alpha isoform levels are decreased in rd1 mice retina respect to their wt counterparts, in concordance with our previous data obtained by immunohistochemistry from retina slices. Noteworthy, RXR activation modulated the mRNA levels of all three RXR isoforms in mixed neuroglial cultures from rd1 retina. Moreover, it also delayed the onset of PhR apoptosis, analyzed by TUNEL assay, and decreased Bax mRNA levels; also decreased GFAP expression of both mRNA and protein level, in Müller glial cells (MGC). Therefore we evaluate whether RXR could regulate anti-inflammatory response in the retina. Our preliminary results suggest that RXR activation increased the transcription of IL-10 in rd1 mixed neuroglial cultures.As a whole, the activation of RXR could promote survival of PhR either by direct action on them, or indirectly by modulating the inflammatory response of MGC.RETINOID X RECEPTORS; RETINA; INFLAMATION; GLIAL MULLER CELLS; SURVIVAL