Exosomes from Retinal Astrocytes Contain Antiangiogenic Components That Inhibit Laser-induced Choroidal Neovascularization

被引：151

作者：

Hajrasouliha, Amir Reza ^{[1
]}

Jiang, Guomin ^{[1
]}

Lu, Qingxian ^{[1
]}

Lu, Huayi ^{[1
]}

Kaplan, Henry J. ^{[1
]}

Zhang, Huang-Ge ^{[2
]}

Shao, Hui ^{[1
]}

机构：

[1] Univ Louisville, Dept Ophthalmol & Visual Sci, Kentucky Lions Eye Ctr, Louisville, KY 40202 USA

[2] Univ Louisville, Dept Res & Dev, Robley Rex Med Ctr, Louisville, KY 40202 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2013年 / 288卷 / 39期

关键词：

MACULAR DEGENERATION; COMPLEMENT ACTIVATION; T-CELLS; ANGIOGENESIS; PROTEINS; IMMUNOTHERAPY; PEPTIDE; GROWTH; MODEL; MICE;

D O I：

10.1074/jbc.M113.470765

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：28058 / 28067

页数：10

共 44 条

[1]

Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration [J].