Genetic Deficiency and Pharmacological Modulation of RORα Regulate Laser-Induced CNV



January 18, 2023

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  • Aging-US published this research paper in Volume 15, Issue 1, entitled, "Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization" by researchers from the Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA; Department of Molecular Medicine, UF Scripps Biomedical Research, Jupiter, FL; BIO5 Institute and Department of Nutritional Sciences, University of Arizona, Tucson, AZ; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL. DOI - Corresponding author - Jing Chen - Abstract Choroidal neovascularization (CNV) causes acute vision loss in neovascular age-related macular degeneration (AMD). Genetic variations of the nuclear receptor RAR-related orphan receptor alpha (RORα) have been linked with neovascular AMD, yet its specific role in pathological CNV development is not entirely clear. In this study, we showed that Rora was highly expressed in the mouse choroid compared with the retina, and genetic loss of RORα in Staggerer mice (Rorasg/sg) led to increased expression levels of Vegfr2 and Tnfa in the choroid and retinal pigment epithelium (RPE) complex. In a mouse model of laser-induced CNV, RORα expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORα in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFα proteins. Pharmacological inhibition of RORα also worsened CNV. In addition, both genetic deficiency and inhibition of RORα substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORα inhibition also promoted angiogenic function of human choroidal endothelial cell culture. Together, our results suggest that RORα negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex. Sign up for free Altmetric alerts about this article - Keywords - age-related macular degeneration, angiogenesis, choroidal neovascularization, inflammation, nuclear receptors, RORα, VEGFR2, TNFα About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: SoundCloud - Facebook - Twitter - Instagram - YouTube - LinkedIn - Pinterest - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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