Asymmetric dimethylarginine aggravates blood-retinal barrier breakdown of diabetic retinopathy via inhibition of intercellular communication in retinal pericytes
Asymmetric dimethylarginine aggravates blood-retinal barrier breakdown of diabetic retinopathy via inhibition of intercellular communication in retinal pericytes
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不对称二甲基精氨酸通过抑制视网膜周细胞的细胞间通讯加剧糖尿病视网膜病变的血-视网膜屏障破坏
DOI：
10.1007/s00726-019-02788-1
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发表时间：
2019-10-01
期刊：
影响因子：
3.5
通讯作者：
Jiang, Jun-Lin
中科院分区：
文献类型：
--
作者：
Huang, Chu-Yi;Zhou, Ting;Jiang, Jun-Lin
血视网膜屏障破坏是糖尿病视网膜病变（DR）的主要病理特征。据报道，不对称二甲基精氨酸（ADMA）在DR患者中升高。在本研究中，我们观察了单次腹腔注射链脲霉素（60 mg/kg）诱导的糖尿病大鼠在2、4和8周时ADMA、视网膜形态和BRB通透性的动态变化，以及d-葡萄糖（30 mM）预处理1、3、5和7天或ADMA（3、10、30 μ M）预处理24、48和72小时的培养大鼠视网膜周细胞。在糖尿病大鼠或培养的视网膜周细胞中检测间隙连接细胞间通讯（GJIC）和血视网膜屏障特异性成分连接蛋白43 （Cx43）的表达，以阐明ADMA是否通过破坏Cx43-GJIC影响血视网膜屏障功能。结果表明，随着糖尿病病程的延长，糖尿病大鼠血视网膜屏障超微结构依次出现细胞连接处损伤、视网膜周细胞凋亡和屏障破坏。糖尿病大鼠和暴露于d-葡萄糖（30 mM）的视网膜周细胞的视网膜通透性、ADMA水平和Cx43表达增加，GJIC异常。使用ADMA或另一种l-精氨酸类似物n - g -单甲基-l-精氨酸或二甲基精氨酸二甲氨基水解酶（DDAHs） siRNA可以观察到类似葡萄糖的作用，这表明ADMA通过破坏Cx43-GJIC加重了血视网膜屏障的破坏。
Blood-retinal barrier breakdown is the main pathological characteristics of diabetic retinopathy (DR). Asymmetric dimethylarginine (ADMA) was reported to be elevated in DR patients. In this study, we observed the dynamic profile of ADMA, retinal morphology and permeability of BRB at 2, 4 or 8 week of diabetic rats induced by a single intraperitoneal injection of streptozocin (60 mg/kg) and in cultured rat retinal pericytes pretreated with d-glucose (30 mM) for 1, 3, 5 and 7 days or ADMA (3, 10, 30 mu M) for 24, 48 and 72 h, trying to explore the effects of ADMA on blood-retinal barrier in DR. Gap junction intercellular communication (GJIC) and the expression of blood-retinal barrier-specific component connexin 43 (Cx43) were examined in diabetic rats or cultured retinal pericytes to elucidate whether ADMA impacted blood-retinal barrier function via damaging Cx43-GJIC. The results showed that with increasing duration of diabetes, the ultrastructure of blood-retinal barrier of diabetic rats appeared cell junction damage, apoptosis of retinal pericytes and breakdown of barrier successively. The increases in retinal permeability, ADMA levels and Cx43 expression, and abnormal GJIC were observed in diabetic rats and retinal pericytes exposed to d-glucose (30 mM). A glucose-like effect was seen using ADMA or another l-arginine analogue N-G-monomethyl-l-arginine or dimethylarginine dimethylaminohydrolases (DDAHs) siRNA, implicating that ADMA aggravated the breakdown of blood-retinal barrier via damaging Cx43-GJIC.