Protective effects of retinoid x receptors on retina pigment epithelium cells.

AYALA PEÑA, V.V.; PILOTTI, F.; VOLONTÉ, Y.A.; ROTSTEIN, N.; POLITI, L.E.; GERMAN, O.L. AUTOR CORRESPONDIENTE

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 1863 p. 1134 - 1145

0167-4889

Age-related macular degeneration (AMD) is among the main pathologies leading to blindness in adults and hascurrently no cure or effective treatment. Selective apoptosis of retina pigment epithelial (RPE) cells results in theprogressive loss of photoreceptor neurons, with the consequent gradual vision loss. Oxidative stress plays animportant role in this process. We have previously determined that activation of RXRs protects rat photoreceptorneurons from oxidative stress- induced apoptosis. In this study we investigated whether RXR ligands preventedapoptosis in an RPE cell line, D407 cells, exposed to hydrogen peroxide (H2O2). H2O2 induced apoptosis of D407cells, promoting p65NFκB nuclear translocation, increasing Bax mRNA expression, activating caspase-3 andaltering cell morphology. We show, for the first time, that HX630, a RXR pan-agonist, protected D407 cells fromH2O2-induced apoptosis, preventing p65NFκB nuclear translocation, increasing Bclxl and PPARγ mRNA levelsand simultaneously decreasing Bax mRNA levels and caspase-3 activation. Pretreatment with a RXR antagonistblocked HX630 protection. LG100754, which binds RXRs but only activates heterodimers and is an antagonist ofRXR homodimers, also had a protective effect. In addition, only agonists known to bind to RXR/PPARγ wereprotective. As a whole, our results suggest that RXR activation protects RPE cells from oxidative stress-inducedapoptosis and this protection might involve signaling through a heterodimeric receptor, such as RXR/PPARγ.These data also imply that RXR agonists might provide potential pharmacological tools for treating retinadegenerative diseases.