Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy
Accumulation of NH2-terminal fragment of connective tissue growth factor in the vitreous of patients with proliferative diabetic retinopathy
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DOI：
10.2337/diacare.27.3.758
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发表时间：
2004-03-01
期刊：
影响因子：
16.2
通讯作者：
Lim, JI
中科院分区：
文献类型：
--
作者：
Hinton, DR;Spee, C;Lim, JI
目的 - 评估增殖性糖尿病视网膜病变 (PDR) 患者玻璃体中结缔组织生长因子 (CTGF) 及其片段的表达，并定位相关视网膜前膜中的 CTGF 表达。 研究设计和方法 - 玻璃体取自 24 名活动性 PDR 患者、4 名静止性 PDR 患者和 23 名患有其他视网膜疾病且无糖尿病的患者，其中 5 名患有糖尿病的患者玻璃体出血。使用酶联免疫吸附测定法测定整个 CTGF 及其 NH2 和 COOH 末端片段的水平。对三名活动性 PDR 患者的视网膜前膜进行免疫组织化学染色，以确定是否存在 CTGF 和细胞类型特异性标记物。 结果-与非糖尿病患者 (P < 0.0001) 或静止性 PDR 患者 (P = 0.02) 的样本相比，活动性 PDR 患者的玻璃体样本中 NH2 末端 CTGF 片段含量显着增加。与患有玻璃体出血的非糖尿病患者的样本相比，患有玻璃体出血的糖尿病患者的玻璃体样本中 NH2 末端 CTGF 的水平也更高（P = 0.02）。所有组中整个 CTGF 的玻璃体水平相似。未检测到 CTGF 的 COOH 末端片段。 CTGF 免疫反应性主要集中于活动性 PDR 膜内的平滑肌肌动蛋白阳性肌成纤维细胞。结论 - 活动性 PDR 患者玻璃体中 NH2 末端 CTGF 片段含量增加，表明其在该疾病中发挥致病作用或代表 CTGF 活性的替代标志物。 CTGF 在肌成纤维细胞中的定位表明诱导纤维化和新血管形成的局部旁分泌机制。
OBJECTIVE- To evaluate the expression of connective tissue growth factor (CTGF) and its fragments in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to localize CTGF expression in associated preretinal membranes.RESEARCH DESIGN AND METHODS- Vitreous was obtained from 24 patients with active PDR, 4 patients with quiescent PDR, and 23 patients with other retinal diseases and no diabetes, including 5 patients with vitreous hemorrhage. Enzyme-linked immunosorbent assay was used to determine levels of whole CTGF and its NH2- and COOH-terminal fragments. Preretinal membranes from three patients with active PDR were stained immunohistochemically for the presence of CTGF and cell type-specific markers.RESULTS- A significant increase in NH2-terminal CTGF fragment content was found in vitreous samples from patients with active PDR when compared with samples from nondiabetic patients (P < 0.0001) or patients with quiescent PDR (P = 0.02). Levels of NH2-terminal CTGF were also greater in vitreous samples from diabetic patients with vitreous hemorrhage compared with samples from nondiabetic patients with vitreous hemorrhage (P = 0.02). Vitreous levels of whole CTGF were similar in all groups. COOH-terminal fragments of CTGF were not detected. CTGF immunoreactivity was predominantly localized to smooth muscle actin-positive myofibroblasts within active PDR membranes.CONCLUSIONS- NH2-terminal CTGF fragment content is increased in the vitreous of patients with active PDR, suggesting that it plays a pathogenic role or represents a surrogate marker of CTGF activity in the disorder. The localization of CTGF in myofibroblasts suggests a local paracrine mechanism for induction of fibrosis and neovascularization.