Connective tissue growth factor as a mediator of intraocular fibrosis
Connective tissue growth factor as a mediator of intraocular fibrosis
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DOI：
10.1167/iovs.07-1302
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Hinton, David R.
中科院分区：
文献类型：
--
作者：
He, Shikun;Chen, Youxin;Hinton, David R.
目的。目的探讨结缔组织生长因子(CTGF)在增生性玻璃体视网膜病变(PVR)发病机制中的作用。方法：采用免疫组织化学方法检测CTGF在PVR膜中的表达，并用ELISA法检测CTGF在玻璃体中的积聚。用实时荧光定量聚合酶链式反应和酶联免疫吸附试验检测CTGF对RPE中I型胶原基因和蛋白表达的影响，用Boyden小室实验检测CTGF对RPE迁移的影响。用兔视网膜色素上皮细胞(RPE细胞)+重组人结缔组织生长因子(RhCTGF)、RPE细胞+血小板源生长因子(RPE细胞+或不加或不加rh CTGF)、RPE细胞感染表达CTGF的腺病毒载体诱导兔实验性PVR。重组人结缔组织生长因子刺激RPE细胞迁移，在50 ng/mL时达到高峰(P<；0.05)，I型胶原表达增加(P<；0.05)。PVR患者玻璃体中CTGF的N端有明显的积聚。单独玻璃体内注射重组人结缔组织生长因子不会产生PVR，而对轻度、非纤维性PVR的兔进行这种注射可以促进致密的、纤维性的视网膜前膜的发展。同样，玻璃体内注射感染了过表达CTGF的腺病毒载体的RPE细胞可诱导纤维性PVR。结论CTGF是视网膜纤维化的主要介质，是PVR治疗PVR的有效靶点。
PURPOSE. To investigate the role of connective tissue growth factor (CTGF) in the pathogenesis of proliferative vitreoretinopathy (PVR).METHODS. Expression of CTGF was evaluated immunohistochemically in human PVR membranes, and the accumulation of CTGF in the vitreous was evaluated by ELISA. The effects of CTGF on type I collagen mRNA and protein expression in RPE were assayed by real-time PCR and ELISA, and migration was assayed with a Boyden chamber assay. Experimental PVR was induced in rabbits with vitreous injection of RPE cells plus rhCTGF; injection of RPE cells plus platelet derived-growth factor, with or without rhCTGF, or by injection of RPE cells infected with an adenoviral vector that expressed CTGF.RESULTS. CTGF was highly expressed in human PVR membranes and partially colocalized with cytokeratin-positive RPE cells. Treatment of RPE with rhCTGF stimulated migration with a peak response at 50 ng/mL (P < 0.05) and increased expression of type I collagen (P < 0.05). There was a prominent accumulation of the N-terminal half of CTGF in the vitreous of patients with PVR. Intravitreous injection of rhCTGF alone did not produce PVR, whereas such injections into rabbits with mild, nonfibrotic PVR promoted the development of dense, fibrotic epiretinal membranes. Similarly, intravitreous injection of RPE cells infected with adenoviral vectors that overexpress CTGF induced fibrotic PVR. Experimental PVR was associated with increased CTGF mRNA in PVR membranes and accumulation of CTGF half fragments in the vitreous.CONCLUSIONS. The results identify CTGF as a major mediator of retinal fibrosis and potentially an effective therapeutic target for PVR.