Abstract
AbstractVascular adhesion molecules play an important role in various immunological disorders, particularly in cancers. However, little is known regarding the role of these adhesion molecules in proliferative retinopathies. We observed that IL-33 regulates VCAM-1 expression in human retinal endothelial cells and that genetic deletion of IL-33 reduces hypoxia-induced VCAM-1 expression and retinal neovascularization in C57BL/6 mice. We found that VCAM-1 via JunB regulates IL-8 promoter activity and expression in human retinal endothelial cells. In addition, our study outlines the regulatory role of VCAM-1-JunB-IL-8 signaling on retinal endothelial cell sprouting and angiogenesis. Our RNA sequencing results show an induced expression of CXCL1 (a murine functional homolog of IL-8) in the hypoxic retina, and intravitreal injection of VCAM-1 siRNA not only decreases hypoxia-induced VCAM-1-JunB-CXCL1 signaling but also reduces OIR-induced sprouting and retinal neovascularization. These findings suggest that VCAM-1-JunB-IL-8 signaling plays a crucial role in retinal neovascularization, and its antagonism might provide an advanced treatment option for proliferative retinopathies.
Funder
U.S. Department of Health & Human Services | NIH | National Eye Institute
Research to Prevent Blindness
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference58 articles.
1. Mutlu, F. M. & Sarici, S. U. Treatment of retinopathy of prematurity: a review of conventional and promising new therapeutic options. Int. J. Ophthalmol. 18, 228–236 (2013).
2. Campochiaro, P. A. Ocular neovascularization. J. Mol. Med. (Berl). 91, 311–321 (2013).
3. Pieramici, D. J. & Rabena, M. D. Anti-VEGF therapy: comparison of current and future agents. Eye (Lond). 22, 1330–1336 (2008).
4. Ciulla, T. A., Hussain, R. M., Taraborelli, D., Pollack, J. S. & Williams, D. F. Longer-term anti-VEGF therapy outcomes in neovascular age-related macular degeneration, diabetic macular edema, and vein occlusion-related macular edema: clinical outcomes in 130 247 eyes. Ophthalmol. Retin. 6, 796–806 (2022).
5. Kuiper, E. J. et al. The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy. PloS One 3, e2675 (2008).
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献