| First Author | Liu CH | Year | 2023 |
| Journal | Aging (Albany NY) | Volume | 15 |
| Issue | 1 | Pages | 37-52 |
| PubMed ID | 36626253 | Mgi Jnum | J:344521 |
| Mgi Id | MGI:7429246 | Doi | 10.18632/aging.204480 |
| Citation | Liu CH, et al. (2023) Genetic deficiency and pharmacological modulation of RORalpha regulate laser-induced choroidal neovascularization. Aging (Albany NY) 15(1):37-52 |
| abstractText | 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 (RORalpha) 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 RORalpha 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, RORalpha expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORalpha in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFalpha proteins. Pharmacological inhibition of RORalpha also worsened CNV. In addition, both genetic deficiency and inhibition of RORalpha substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORalpha inhibition also promoted angiogenic function of human choroidal endothelial cell culture. Together, our results suggest that RORalpha negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex. |
