Exosomes from Retinal Astrocytes Contain Antiangiogenic Components That Inhibit Laser-induced Choroidal Neovascularization |
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| Authors: | Amir Reza Hajrasouliha Guomin Jiang Qingxian Lu Huayi Lu Henry J Kaplan Huang-Ge Zhang Hui Shao |
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| Institution: | From the ‡Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center and ;the §Department of Research and Development, Robley Rex Medical Center, University of Louisville, Louisville, Kentucky 40202 |
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| Abstract: | Exosomes released from different types of host cells have different biological effects. We report that exosomes released from retinal astroglial cells (RACs) suppress retinal vessel leakage and inhibit choroidal neovascularization (CNV) in a laser-induced CNV model, whereas exosomes released from retinal pigmental epithelium do not. RAC exosomes inhibit the migration of macrophages and the tubule forming of mouse retinal microvascular endothelial cells. Further, we analyzed antiangiogenic components in RAC exosomes using an angiogenesis array kit and detected several endogenous inhibitors of angiogenesis exclusively present in RAC exosomes, such as endostatin. Moreover, blockade of matrix metalloproteinases in the cleavage of collagen XVIII to form endostatin using FN-439 reverses RAC exosome-mediated retinal vessel leakage. This study demonstrates that exosomes released from retinal tissue cells have different angiogenic effects, with exosomes from RACs containing antiangiogenic components that might protect the eye from angiogenesis and maintain its functional integrity. In addition, by identifying additional components and their functions of RAC exosomes, we might improve the antiangiogenic therapy for CNV in age-related macular degeneration and diabetic retinopathy. |
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| Keywords: | Angiogenesis Endothelial Cell Exosomes Inflammation Macrophages Vascular Endothelial Growth Factor (VEGF) Age-related Macular Degeneration Choroidal Neovascularization Retinal Astrocytes Retinal Pigmental Epithelium |
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