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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >Muller cell-derived VEGF is a significant contributor to retinal neovascularization.
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Muller cell-derived VEGF is a significant contributor to retinal neovascularization.

机译：穆勒细胞衍生的VEGF是视网膜新生血管形成的重要因素。

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Vascular endothelial growth factor (VEGF-A) is a major pathogenic factor and a therapeutic target for age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. Despite intensive effort in the field, the cellular mechanisms of VEGF action remain virtually uninvestigated. This situation makes it difficult to design cellular target-based therapeutics for these diseases. In light of the recent finding that VEGF is a potential neurotrophic factor, revealing the cellular mechanisms of VEGF action becomes necessary to preserve its beneficial effect and inhibit its pathological function in long-term anti-VEGF therapeutics for ocular vascular diseases. We therefore generated conditional VEGF knockout mice with an inducible Cre/lox system and determined the significance of Muller cell-derived VEGF in retinal development and maintenance and ischaemia-induced neovascularizartion and vascular leakage. Retinal development in the conditional VEGF knockout mice was analysed by examining retinal and choroidal vasculatures and retinal morphology and function. Ischaemia-induced retinal neovascularization and vascular leakage in the conditional VEGF knockout mice were analysed with fluorescein angiography, quantification of proliferative neovascular cells, immunohistochemistry, and immunoblotting using an oxygen-induced retinopathy model. Our results demonstrated that disruption of Muller cell-derived VEGF resulted in no apparent defects in retinal and choroidal vasculatures and retinal morphology and function, significant inhibition of the ischaemia-induced retinal neovascularization and vascular leakage, and attenuation of the ischaemia-induced breakdown of the blood-retina barrier. These results suggest that the retinal Muller cell-derived VEGF is a major contributor to ischaemia-induced retinal vascular leakage and pre-retinal and intra-retinal neovascularization. The observation that a significant, but not complete, reduction of VEGF in the retina does not cause detectable retinal degeneration suggests that appropriate doses of anti-VEGF agents may be important to the safe treatment of retinal vascular diseases.
机译：血管内皮生长因子（VEGF-A）是年龄相关性黄斑变性，糖尿病性视网膜病和早产儿视网膜病的主要致病因素和治疗靶标。尽管在该领域付出了巨大的努力，但VEGF作用的细胞机制实际上仍未得到研究。这种情况使设计针对这些疾病的基于细胞靶标的疗法变得困难。根据最近的发现，VEGF是潜在的神经营养因子，揭示VEGF作用的细胞机制对于维持其有益作用并抑制其在长期抗VEGF治疗眼血管疾病中的作用是必要的。因此，我们产生了具有可诱导的Cre / lox系统的条件性VEGF基因敲除小鼠，并确定了Muller细胞来源的VEGF在视网膜发育和维持以及缺血引起的新血管形成和血管渗漏中的重要性。通过检查视网膜和脉络膜脉管系统以及视网膜形态和功能来分析条件性VEGF基因敲除小鼠的视网膜发育。使用荧光素血管造影术，增生性新血管细胞的定量，免疫组织化学和使用氧诱导性视网膜病变模型的免疫印迹分析条件性VEGF基因敲除小鼠的局部缺血诱导的视网膜新血管形成和血管渗漏。我们的研究结果表明，Muller细胞源性VEGF的破坏不会导致视网膜和脉络膜脉管系统以及视网膜形态和功能的明显缺陷，对缺血引起的视网膜新血管形成和血管渗漏的抑制作用明显，并且缺血导致的缺血性破坏的减弱血视网膜屏障。这些结果表明，视网膜穆勒细胞衍生的VEGF是局部缺血引起的视网膜血管渗漏以及视网膜前和视网膜内新血管形成的主要贡献者。观察到视网膜中的VEGF显着但不完全减少不会导致可检测到的视网膜变性，这表明适当剂量的抗VEGF剂可能对安全治疗视网膜血管疾病很重要。

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