Brar Vikram S, Sharma Rajesh K, Murthy Ravi K, Chalam K V
University of Florida College of Medicine, Department of Ophthalmology Jacksonville, FL 32209, USA.
Mol Vis. 2010 Sep 12;16:1848-53.
Vascular endothelial growth factor (VEGF) is well known for its role in pathologic neovascularization, including wet age-related macular degeneration. However, a growing body of evidence indicates that VEGF is also neuroprotective of non-vascular cells in various animal models through reduction of oxidative stress. In light of the widespread use of intraocular anti-VEGF therapies for age-related macular degeneration (AMD), we evaluated the impact of anti-VEGF agents on the neuroprotective effect of VEGF on retinal ganglion cells.
Staurosporine differentiated retinal ganglion cells were treated with increasing doses of VEGF in the presence of hydrogen peroxide. After optimization, an increasing concentration of bevacizumab was added to neutralize VEGF-mediated protection. The degree of oxidative damage was measured at various time points using buthionine sulfoxime (BSO), a glutathione reductase inhibitor. Cell viability was assessed using WST-1 and Crystal violet assays.
VEGF (200 ng/ml) protected differentiated retinal ganglion cells (RGC)-5 against H(2)0(2)-mediated oxidative stress. This effect was eliminated by co-treatment with bevacizumab (2.0 mg/ml), which by itself was not cytotoxic.
These results indicate an important role for VEGF in the maintenance of retinal ganglion cells.
血管内皮生长因子（VEGF）在病理性新生血管形成中所起的作用已广为人知，包括湿性年龄相关性黄斑变性。然而，越来越多的证据表明，在各种动物模型中，VEGF还可通过减轻氧化应激对非血管细胞起到神经保护作用。鉴于眼内抗VEGF疗法在年龄相关性黄斑变性（AMD）中的广泛应用，我们评估了抗VEGF药物对VEGF对视网膜神经节细胞神经保护作用的影响。
在过氧化氢存在的情况下，用递增剂量的VEGF处理经星形孢菌素分化的视网膜神经节细胞。优化后，添加递增浓度的贝伐单抗以中和VEGF介导的保护作用。使用谷胱甘肽还原酶抑制剂丁硫氨酸亚砜胺（BSO）在不同时间点测量氧化损伤程度。使用WST-1和结晶紫测定法评估细胞活力。
VEGF（200 ng/ml）保护分化的视网膜神经节细胞（RGC）-5免受H₂O₂介导的氧化应激。与贝伐单抗（2.0 mg/ml）共同处理可消除这种作用，而贝伐单抗本身无细胞毒性。
这些结果表明VEGF在维持视网膜神经节细胞方面具有重要作用。
