Sene Abdoulaye, Chin-Yee David, Apte Rajendra S
Department of Ophthalmology, Washington University School of Medicine, St Louis, MO, USA.
Department of Ophthalmology, Washington University School of Medicine, St Louis, MO, USA.
Trends Mol Med. 2015 Jan;21(1):43-51. doi: 10.1016/j.molmed.2014.10.005. Epub 2014 Nov 1.
The central role of vascular endothelial growth factor (VEGF) signaling in regulating normal vascular development and pathological angiogenesis has been documented in multiple studies. Ocular anti-VEGF therapy is highly effective for treating a subset of patients with blinding eye disorders such as diabetic retinopathy and neovascular age-related macular degeneration (AMD). However, chronic VEGF suppression can lead to adverse effects associated with poor visual outcomes due to the loss of prosurvival and neurotrophic capacities of VEGF. In this review, we discuss emerging evidence for immune-related mechanisms that regulate ocular angiogenesis in a VEGF-independent manner. These novel molecular and cellular pathways may provide potential therapeutic avenues for a multitarget strategy, preserving the neuroprotective functions of VEGF in those patients whose disease is unresponsive to VEGF neutralization.
血管内皮生长因子(VEGF)信号传导在调节正常血管发育和病理性血管生成中的核心作用已在多项研究中得到证实。眼部抗VEGF治疗对治疗一部分患有致盲性眼病(如糖尿病性视网膜病变和新生血管性年龄相关性黄斑变性(AMD))的患者非常有效。然而,由于VEGF的促生存和神经营养能力丧失,长期抑制VEGF会导致与视力不佳相关的不良反应。在这篇综述中,我们讨论了以VEGF非依赖性方式调节眼部血管生成的免疫相关机制的新证据。这些新的分子和细胞途径可能为多靶点策略提供潜在的治疗途径,在那些对VEGF中和无反应的患者中保留VEGF的神经保护功能。