Leitch Ian M, Gerometta Michael, Eichenbaum David, Finger Robert P, Steinle Nathan C, Baldwin Megan E
Opthea Limited, 650 Chapel Street, Level 4, Melbourne, VIC, 3141, Australia.
Retina Vitreous Associates of Florida, St. Petersburg, FL, 33711, USA.
Ophthalmol Ther. 2024 Jul;13(7):1857-1875. doi: 10.1007/s40123-024-00973-4. Epub 2024 Jun 1.
The development of treatments targeting the vascular endothelial growth factor (VEGF) signaling pathways have traditionally been firstly investigated in oncology and then advanced into retinal disease indications. Members of the VEGF family of endogenous ligands and their respective receptors play a central role in vasculogenesis and angiogenesis during both development and physiological homeostasis. They can also play a pathogenic role in cancer and retinal diseases. Therapeutic approaches have mostly focused on targeting VEGF-A signaling; however, research has shown that VEGF-C and VEGF-D signaling pathways are also important to the disease pathogenesis of tumors and retinal diseases. This review highlights the important therapeutic advances and the remaining unmet need for improved therapies targeting additional mechanisms beyond VEGF-A. Additionally, it provides an overview of alternative VEGF-C and VEGF-D signaling involvement in both health and disease, highlighting their key contributions in the multifactorial pathophysiology of retinal disease including neovascular age-related macular degeneration (nAMD). Strategies for targeting VEGF-C/-D signaling pathways will also be reviewed, with an emphasis on agents currently being developed for the treatment of nAMD.
针对血管内皮生长因子（VEGF）信号通路的治疗方法传统上首先在肿瘤学领域进行研究，然后才推进到视网膜疾病适应症。内源性配体的VEGF家族成员及其各自的受体在发育和生理稳态过程中的血管生成和血管新生中起核心作用。它们在癌症和视网膜疾病中也可发挥致病作用。治疗方法大多集中在靶向VEGF-A信号传导；然而，研究表明，VEGF-C和VEGF-D信号通路对肿瘤和视网膜疾病的发病机制也很重要。本综述重点介绍了重要的治疗进展以及针对VEGF-A以外的其他机制进行改进治疗的尚未满足的需求。此外，它概述了VEGF-C和VEGF-D信号在健康和疾病中的替代作用，强调了它们在包括新生血管性年龄相关性黄斑变性（nAMD）在内的视网膜疾病多因素病理生理学中的关键作用。还将综述靶向VEGF-C/-D信号通路的策略，重点是目前正在开发用于治疗nAMD的药物。
