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

TURPAUD, AXEL; VOLONTÉ, Y.A.; AYALA PEÑA, V.B.; GARELLI, A.; ROTSTEIN, N.; POLITI, L.; GERMAN, O.L.

Congreso; SAN 2018; 2018

Retinal neurodegenerative diseases, which have no effective treatments, share as a finalcommon step the photoreceptor cells (PhR) death. Also inflammation has a role in thesepathologies. Retinoid X receptors (RXR) have the capacity of modulate and integratemultiple cell functions; and their activation has shown beneficial clinical effects in animalmodels of chronic inflammatory diseases. In this work we assessed whether this receptorsmight 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 rd1mice retina respect to their wt counterparts, in concordance with our previous data obtainedby immunohistochemistry from retina slices. Noteworthy, RXR activation modulated themRNA 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, anddecreased Bax mRNA levels; also decreased GFAP expression of both mRNA and proteinlevel, in Müller glial cells (MGC). Therefore we evaluate whether RXR could regulate antiinflammatoryresponse in the retina. Our preliminary results suggest that RXR activationincreased 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 onthem, or indirectly by modulating the inflammatory response of MGC.