Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

黄斑变性 肝细胞生长因子 医学 视网膜色素上皮 血管抑制剂 癌症研究 血管内皮生长因子 碱性成纤维细胞生长因子 血管生成 胎盘生长因子 脉络膜新生血管 生长因子 成纤维细胞生长因子 免疫学 视网膜 贝伐单抗 眼科 内科学 受体 化疗 血管内皮生长因子受体
作者
João Rafael de Oliveira Dias,Eduardo B. Rodrigues,Maurício Maia,Octaviano Magalhães,Fernando M. Penha,Michel Eid Farah
出处
期刊:British Journal of Ophthalmology [BMJ]
卷期号:95 (12): 1631-1637 被引量:99
标识
DOI:10.1136/bjo.2010.186361
摘要

The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

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