Exosomes from retinal astrocytes contain antiangiogenic components that inhibit laser-induced choroidal neovascularization.
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.
From the Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center and.
Amir Reza
AR
Hajrasouliha
Guomin
G
Jiang
Qingxian
Q
Lu
Huayi
H
Lu
Henry J
HJ
Kaplan
Huang-Ge
HG
Zhang
Hui
H
Shao
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D020256:Choroidal Neovascularization / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D007249:Inflammation; D007834:Lasers; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D012160:Retina / Q000166:cytology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A
Age-related Macular Degeneration; Angiogenesis; Choroidal Neovascularization; Endothelial Cell; Exosomes; Inflammation; Macrophages; Retinal Astrocytes; Retinal Pigmental Epithelium; Vascular Endothelial Growth Factor (VEGF)