Sharma Rajesh K, Rogojina Anna T, Chalam K V
Department of Ophthalmology, University of Florida, College of Medicine, Jacksonville FL, USA.
Mol Vis. 2010 Oct 27;16:2175-84.
Vascular endothelial growth factor (VEGF) plays a key role in neovascularization by stimulating the proliferation and migration of vascular endothelial cells. The anti-VEGF therapy bevacizumab acts by binding to VEGF and preventing its effects. However, this linear interaction represents only a partial view of the pathobiology of neovascular diseases and the anti-VEGF treatment. To obtain an integrated view of the processes involved in VEGF-related ocular pathologies, we applied a systems approach and investigated whether intravitreal bevacizumab injections have a global effect in normalizing the ocular physiology perturbed by the disease.
We analyzed 90 analytes representing various pathophysiological processes in aqueous humor. The samples were obtained from eight patients receiving intravitreal bevacizumab injections for various ocular VEGF-related conditions. The samples were obtained before and after the injection and were analyzed using microbead technology developed by Luminex xMAP.
Forty-three analytes were detected above the sensitivity of the assay both in pre- and post-injection samples. Of these, normal values of 41 analytes were known and these analytes were further analyzed. The detected analytes included relevant markers such as VEGF, C reactive protein, glutathione, and cytokines. We identified 24 markers that were perturbed more than 1.5 fold in diseased samples (pre-injection) compared to normal levels. The levels of perturbed analytes were compared in post-treatment samples. The results demonstrated an unequivocal trend toward normalization in post-treatment samples.
Our results show intraocular bevacizumab injections change the perturbed physiologic environment of the eye toward normalization. Its effects reached beyond neutralizing VEGF. The results also demonstrate that large-scale analysis of the aqueous, using a systems approach, could provide useful insight regarding ocular diseases, their pathophysiologies, and treatment responses.
血管内皮生长因子（VEGF）通过刺激血管内皮细胞的增殖和迁移在新生血管形成中起关键作用。抗VEGF疗法贝伐单抗通过与VEGF结合并阻止其作用来发挥功效。然而，这种线性相互作用仅代表了新生血管疾病和抗VEGF治疗病理生物学的部分观点。为了全面了解VEGF相关眼部疾病所涉及的过程，我们采用了系统方法，并研究玻璃体内注射贝伐单抗是否对使受疾病干扰的眼部生理恢复正常具有全面影响。
我们分析了代表房水各种病理生理过程的90种分析物。样本取自八名因各种与眼部VEGF相关病症接受玻璃体内贝伐单抗注射的患者。在注射前和注射后获取样本，并使用Luminex xMAP开发的微珠技术进行分析。
在注射前和注射后样本中均检测到43种分析物高于检测灵敏度。其中，41种分析物的正常值已知，并对这些分析物进行了进一步分析。检测到的分析物包括相关标志物，如VEGF、C反应蛋白、谷胱甘肽和细胞因子。我们确定了24种标志物，与正常水平相比，在患病样本（注射前）中其扰动超过1.5倍。在治疗后样本中比较了受扰动分析物的水平。结果表明治疗后样本呈现出明确的恢复正常的趋势。
我们的结果表明玻璃体内注射贝伐单抗可使受扰动的眼部生理环境恢复正常。其作用不仅限于中和VEGF。结果还表明，采用系统方法对房水进行大规模分析可为眼部疾病、其病理生理学和治疗反应提供有用的见解。
