Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Mayur ChoudharyGoldis Malek

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model. Herein we tested the therapeutic impact of AhR activation on CNV lesion formation and factors associated with aberrant neovascularization. We screened a panel of synthetic drugs and endogenous AhR ligands, assessed their ability to activate AhR in choroidal endothelial cells, and inhibit angiogenesis in vitro. Drugs with an anti-angiogenic profile were then administered to a murine model of CNV. Two compounds, leflunomide and flutamide, significantly inhibited CNV formation concurrent with positive modifying effects on angiogenesis, inflammation, extracellular matrix remodeling, and fibrosis. These results validate the role of the AhR pathway in regulating CNV pathogenesis, identif...Continue Reading

Citations

Jun 10, 2020·Investigative Ophthalmology & Visual Science·Jeremy Peavey, Goldis Malek
Sep 17, 2020·International Journal of Molecular Sciences·Stephen SafeArul Jayaraman
Apr 25, 2020·International Journal of Molecular Sciences·Pei-Li YaoGoldis Malek
Sep 20, 2020·International Journal of Molecular Sciences·Mayur Choudhary, Goldis Malek
Aug 15, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Michael LekwuwaGoldis Malek

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