Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway.
Plasma Exosomes Contribute to Microvascular Damage in Diabetic Retinopathy by Activating the Classical Complement Pathway.
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作者：
Huang C;Fisher KP;Hammer SS;Navitskaya S;Blanchard GJ;Busik JV
糖尿病视网膜病变（DR）是糖尿病的微血管并发症，是工作年龄成人视力丧失的主要原因。最近的研究表明，补体系统在血管损伤和DR进展中起着重要作用。然而，补体系统在DR中的作用和激活尚不清楚。外泌体，分泌到细胞外环境中的小泡，具有血浆中补体蛋白的货物，这表明它们可以参与引起与DR相关的血管损伤。我们证明，血浆中载有IgG的外泌体激活经典补体途径，并且这些外泌体的数量在糖尿病中增加。此外，我们表明，在糖尿病小鼠的外泌体中缺乏IgG导致视网膜血管损伤减少。本研究的结果表明，载IgG的血浆外泌体的补体激活可能有助于DR的发展。
Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in working-age adults. Recent studies have implicated the complement system as a player in the development of vascular damage and progression of DR. However, the role and activation of the complement system in DR are not well understood. Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma, suggesting that they can participate in causing the vascular damage associated with DR. We demonstrate that IgG-laden exosomes in plasma activate the classical complement pathway and that the quantity of these exosomes is increased in diabetes. Moreover, we show that a lack of IgG in exosomes in diabetic mice results in a reduction in retinal vascular damage. The results of this study demonstrate that complement activation by IgG-laden plasma exosomes could contribute to the development of DR.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
9
作者：
Clark SJ;Bishop PN
通讯作者：
Bishop PN
影响因子：
4.6
作者：
Klingeborn M;Dismuke WM;Skiba NP;Kelly U;Stamer WD;Bowes Rickman C
通讯作者：
Bowes Rickman C
影响因子：
3.6
作者：
Biro, Adrienn;Thielens, Nicole M.;Arlaud, Gerard J.
通讯作者：
Arlaud, Gerard J.
影响因子：
3.4
作者：
Kalra, Hina;Adda, Christopher G.;Mathivanan, Suresh
通讯作者：
Mathivanan, Suresh