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Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor
| Content Provider | Scilit |
|---|---|
| Author | Choudhary, Mayur Safe, Stephen Malek, Goldis |
| Copyright Year | 2018 |
| Description | Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 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, identify mechanisms of AhR-based therapies in the eye, and argue in favor of developing AhR as a drug target for the treatment of neovascular AMD. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880720/pdf |
| Ending Page | 1595 |
| Page Count | 13 |
| Starting Page | 1583 |
| ISSN | 09254439 |
| e-ISSN | 1879260X |
| DOI | 10.1016/j.bbadis.2018.02.015 |
| Journal | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease |
| Issue Number | 5 |
| Volume Number | 1864 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-05-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Aryl Hydrocarbon Receptor Choroidal Neovascularization Extracellular Matrix Selective Receptor Modulators |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Biology Molecular Medicine |
