A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy.
A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy.
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DOI：
10.1136/bjophthalmol-2011-301005
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Schlingemann RO
中科院分区：
文献类型：
--
作者：
Van Geest RJ;Lesnik-Oberstein SY;Tan HS;Mura M;Goldschmeding R;Van Noorden CJ;Klaassen I;Schlingemann RO
在增殖性糖尿病视网膜病变（PDR）中，血管内皮生长因子（VEGF）和结缔组织生长因子（CTGF）可通过新生血管形成导致失明，随后视网膜纤维化。之前的研究表明，眼睛中CTGF和VEGF水平平衡的改变与这种血管纤维化开关有关。本研究探讨抗vegf药物是否如该模型预测的那样，诱导PDR患者加速纤维化。采用ELISA法检测52例PDR患者玻璃体样本的CTGF和VEGF水平，其中24例患者在玻璃体切除术前1周至3个月接受了玻璃体内贝伐单抗治疗，CTGF和VEGF水平与临床及术中玻璃体视网膜纤维化程度相关。CTGF与纤维化程度呈正相关，VEGF与纤维化程度负相关。CTGF/VEGF比值是纤维化的最强预测因子。临床上，玻璃体内注射贝伐单抗后观察到纤维化增加。这些结果证实了CTGF/VEGF比值是PDR玻璃体视网膜纤维化的一个强有力的预测因子，并表明玻璃体内抗VEGF治疗导致PDR患者纤维化增加。这些发现为CTGF和VEGF平衡决定血管纤维化开关的模型提供了强有力的支持，并确定了CTGF在PDR临床管理中的可能的治疗靶点。
In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) may cause blindness by neovascularisation followed by fibrosis of the retina. It has previously been shown that a shift in the balance between levels of CTGF and VEGF in the eye is associated with this angiofibrotic switch. This study investigated whether anti-VEGF agents induce accelerated fibrosis in patients with PDR, as predicted by this model. CTGF and VEGF levels were measured by ELISA in 52 vitreous samples of PDR patients, of which 24 patients had received intravitreal bevacizumab 1 week to 3 months before vitrectomy, and were correlated with the degree of vitreoretinal fibrosis as determined clinically and intra-operatively. CTGF correlated positively, and VEGF correlated negatively with the degree of fibrosis. The CTGF/VEGF ratio was the strongest predictor of fibrosis. Clinically, increased fibrosis was observed after intravitreal bevacizumab. These results confirm that the CTGF/VEGF ratio is a strong predictor of vitreoretinal fibrosis in PDR, and show that intravitreal anti-VEGF treatment causes increased fibrosis in PDR patients. These findings provide strong support for the model that the balance of CTGF and VEGF determines the angiofibrotic switch, and identify CTGF as a possible therapeutic target in the clinical management of PDR.
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