Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization

Chi Hsiu Liu, Felix Yemanyi, Kiran Bora, Neetu Kushwah, Alexandra K. Blomfield, Theodore M. Kamenecka, John Paul SanGiovanni, Ye Sun, Laura A. Solt, Jing Chen

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)37-52
Number of pages16
Issue number1
StatePublished - 2023


  • Age-related macular degeneration
  • Angiogenesis
  • Choroidal neovascularization
  • Inflammation
  • Nuclear receptors
  • Rorα
  • Tnfα
  • Vegfr2

ASJC Scopus subject areas

  • Aging
  • Cell Biology


Dive into the research topics of 'Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization'. Together they form a unique fingerprint.

Cite this