Paris-Cardiovascular Research Centre, Inserm U970, Paris, France.
Diabetes. 2010 Mar;59(3):694-701. doi: 10.2337/db08-1524. Epub 2009 Dec 15.
Diabetic retinopathy is associated with progressive retinal capillary activation and proliferation, leading to vision impairment and blindness. Microparticles are submicron membrane vesicles with biological activities, released following cell activation or apoptosis. We tested the hypothesis that proangiogenic microparticles accumulate in vitreous fluid in diabetic retinopathy.
Levels and cellular origin of vitreous and plasma microparticles from control (n = 26) and diabetic (n = 104) patients were analyzed by flow cytometry, and their proangiogenic activity was assessed by in vitro thymidine incorporation and neovessel formation in subcutaneous Matrigel plugs in mice.
Microparticles of endothelial, platelet, photoreceptor, and microglial origin were identified in vitreous samples. Levels of photoreceptor and microglial microparticles were undetectable in plasmas but were comparable in diabetic and control vitreous samples. Vitreous platelet and endothelial microparticles levels were increased in diabetic patients and decreased following panretinal laser photocoagulation or intravitreal antivascular endothelial growth factor injection in proliferative diabetic retinopathy (PDR). The ratio of vitreous to plasma microparticle levels was calculated to estimate local formation versus potential plasma leakage. In PDR, the endothelial microparticles ratio--but not that for platelet--was greater than 1.0, indicating local formation of endothelial microparticles from retinal vessels and permeation of platelet microparticles from plasma. Isolated vitreous microparticles stimulated by 1.6-fold endothelial proliferation and increased new vessel formation in mice.
The present study demonstrates that vitreous fluid contains shed membrane microparticles of endothelial, platelet, and retinal origin. Vitreous microparticles levels are increased in patients with diabetic retinopathy, where they could contribute to disease progression.
糖尿病性视网膜病变与视网膜毛细血管的渐进性激活和增殖有关，导致视力损害和失明。微粒是具有生物活性的亚微米膜囊泡，在细胞激活或凋亡后释放。我们检验了这样一个假说，即在糖尿病性视网膜病变中，促血管生成的微粒会在玻璃体中蓄积。
通过流式细胞术分析来自对照（n=26）和糖尿病（n=104）患者的玻璃体和血浆微粒的水平和细胞来源，并通过体外胸苷掺入和在小鼠皮下 Matrigel 塞中形成新血管来评估其促血管生成活性。
在玻璃体样本中鉴定出内皮细胞、血小板、光感受器和小胶质细胞来源的微粒。在血浆中无法检测到光感受器和小胶质细胞来源的微粒，但在糖尿病和对照玻璃体样本中它们的水平相当。血小板和内皮细胞微粒的水平在糖尿病患者中增加，并在增殖性糖尿病性视网膜病变（PDR）中接受全视网膜激光光凝或玻璃体内抗血管内皮生长因子注射后降低。计算玻璃体与血浆微粒水平的比值，以估计局部形成与潜在的血浆渗漏。在 PDR 中，内皮细胞微粒的比值（而不是血小板）大于 1.0，表明内皮细胞微粒来自视网膜血管的局部形成和血小板微粒从血浆的渗透。分离的玻璃体微粒在 1.6 倍的内皮细胞增殖刺激下，可在小鼠中刺激新血管形成。
本研究表明，玻璃体中含有来自内皮细胞、血小板和视网膜的脱落膜微粒。糖尿病性视网膜病变患者的玻璃体微粒水平升高，它们可能有助于疾病的进展。
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