Bibliographic Details
| Title: |
A novel retinoic acid drug, EYE-502, inhibits choroidal neovascularization by targeting endothelial cells and pericytes. |
| Authors: |
Shen, Yaming1 (AUTHOR), Xu, Miao1 (AUTHOR), Ren, Ling2 (AUTHOR), Li, Xiumiao3 (AUTHOR), Han, Xiaoyan2 (AUTHOR), Cao, Xin4 (AUTHOR) caox@fudan.edu.cn, Yao, Jin1,3 (AUTHOR) jinyao1972@126.com, Yan, Biao2 (AUTHOR) biao.yan@fdeent.org |
| Source: |
Scientific Reports. 6/27/2023, Vol. 13 Issue 1, p1-16. 16p. |
| Subject Terms: |
*RANIBIZUMAB, *ENDOTHELIAL cells, *TRETINOIN, *PERICYTES, *MACULAR degeneration, *RETINOIC acid receptors, *NEOVASCULARIZATION |
| Abstract: |
Choroidal neovascularization (CNV) occurs in neovascular age-related macular degeneration (AMD) and often leads to permanent visual impairment. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is the gold standard for the treatment of CNV. However, anti-VEGF treatment did not always cause vision improvement and sometimes had detrimental effects on normal retinal tissues. Herein, we identified a novel retinoic acid drug, EYE-502, which had great therapeutic effects on CNV. Administration of EYE-502 could inhibit VEGF-induced dysfunction of endothelial cells (ECs) and reduce platelet-derived growth factor (PDGF)-induced recruitment of pericytes to ECs in vitro. Administration of EYE-502 could reduce the area of choroidal sprouting and laser-induced CNV, exhibiting similar anti-angiogenic effects as aflibercept. Moreover, administration of EYE-502 could reduce pericyte coverage in the sprouting vessels and choroidal neovascularization. Mechanistically, EYE-502 primarily bound to retinoic acid receptors (RARs) and exerted the anti-angiogenic effects by targeting ECs and pericytes via affecting the activation of Wnt/β-catenin and PDGF/PDGFR/PI3K/Akt signaling. Taken together, this study reports a novel retinoic acid drug, EYE-502, which can exert the anti-angiogenic effects by simultaneous targeting of ECs and pericytes. [ABSTRACT FROM AUTHOR] |
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