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• W3181569341 endingPage "119098" @default.
• W3181569341 startingPage "119098" @default.
• W3181569341 abstract "Photoreceptor cell (PHR) death is a hallmark of most retinal neurodegenerative diseases, in which inflammation plays a critical role. Activation of retinoid X receptors (RXR) modulates and integrates multiple cell functions, and has beneficial effects in animal models of chronic inflammatory diseases. Nonetheless, the mechanisms involved and their role in retina neuroprotection are poorly understood. In this work we assessed whether RXR activation prevents inflammation and/or PHR death in retinitis pigmentosa, an inherited retina neurodegeneration, using as an ex vivo model, retinas from the rd1 mice, a murine model of this disease. We demonstrated that rd1 retinas had lower levels of RXR alpha isoform than their wt counterparts at early developmental times, whereas its distribution pattern remained similar. In mixed neuro-glial cultures obtained from either rd1 or wt retinas, both PHR and Müller glial cells (MGC) expressed RXRalpha, and RXR activation by its synthetic pan-agonist PA024 selectively increased mRNA levels of RXRgamma isoform. PA024 decreased PHR death in rd1 mixed cultures; it reduced the amount of non-viable neurons, delayed the onset of PHR apoptosis, and decreased Bax mRNA levels. PA024 also reduced MGC reactivity in vitro before and at the onset of degeneration, decreasing GFAP expression, increasing glutamine synthetase mRNA levels, and promoting the transcription of the anti-inflammatory cytokine, Il-10. These results suggest that RXR activation rescues rd1 PHR and decreases MGC reactivity, promoting an anti-inflammatory environment in the rd1 retina, thus supporting the potential of RXR agonists as pharmacological tools for treating retina degenerative diseases. • RXR alpha expression was altered in the rd1 retina. • The pan-RXR agonist PA024 promoted rd1 PHR survival in retina neuro-glial cultures. • PA024 protected rd1 PHR from apoptosis and reduced Bax expression • PA024 reduced MGC reactivity decreasing GFAP and increasing Gs expression. • PA024 restored Il-10 mRNA levels, which were decreased in rd1 neuro-glial cultures." @default.
• W3181569341 created "2021-07-19" @default.
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• W3181569341 date "2021-10-01" @default.
• W3181569341 modified "2023-10-06" @default.
• W3181569341 title "Retinoid X receptor activation promotes photoreceptor survival and modulates the inflammatory response in a mouse model of retinitis pigmentosa" @default.
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• W3181569341 doi "https://doi.org/10.1016/j.bbamcr.2021.119098" @default.
• W3181569341 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34271041" @default.
• W3181569341 hasPublicationYear "2021" @default.
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