The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210029, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210029, China.
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210029, China; The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing 210029, China.
Biomed Pharmacother. 2021 Jun;138:111493. doi: 10.1016/j.biopha.2021.111493. Epub 2021 Mar 16.
Ocular neovascularization is a devastating pathology observed in numerous ocular diseases and is a major cause of blindness. However, all current treatments have their limitations. Hence, it is important to explore new therapeutic strategies. This study aimed to investigate the role of anlotinib, a small molecular multi-targeting tyrosine kinase inhibitor, in ocular neovascularization. Anlotinib administration did not induce any cytotoxicity and tissue toxicity at the tested concentrations. Cellular functional experiments demonstrated that anlotinib inhibited the viability, proliferation, migration, and tube formation ability of endothelial cells (ECs) and pericytes. Western blot analysis demonstrated that anlotinib significantly inhibited the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor β (PDGFR-β), as well as their downstream signaling pathways stimulated by VEGF or PDGF-BB, in a concentration-dependent manner in ECs and pericytes. Using an oxygen-induced retinopathy (OIR) model, our results demonstrated that injection of anlotinib reduced avascular areas and pathological neovascular tufts. Furthermore, using a laser-induced choroidal neovascularization (CNV) model, we observed that the combined treatment of anlotinib and Lucentis reduced the size and thickness of CNV lesions compared to Lucentis monotherapy alone. Taken together, our results suggest that anlotinib could be a promising drug candidate for ocular neovascularization.
眼内新生血管是多种眼部疾病中观察到的一种破坏性病理，是导致失明的主要原因。然而，所有现有的治疗方法都有其局限性。因此，探索新的治疗策略很重要。本研究旨在探讨安罗替尼（一种小分子多靶点酪氨酸激酶抑制剂）在眼内新生血管中的作用。在测试浓度下，安罗替尼给药不会引起细胞毒性和组织毒性。细胞功能实验表明，安罗替尼抑制内皮细胞（EC）和成纤维细胞的活力、增殖、迁移和管腔形成能力。Western blot 分析表明，安罗替尼以浓度依赖的方式显著抑制 VEGF 或 PDGF-BB 刺激的 EC 和成纤维细胞中血管内皮生长因子受体 2（VEGFR2）和血小板衍生生长因子受体β（PDGFR-β）的磷酸化及其下游信号通路。利用氧诱导的视网膜病变（OIR）模型，我们的结果表明，安罗替尼注射减少了无血管区和病理性新生血管丛。此外，利用激光诱导脉络膜新生血管（CNV）模型，我们观察到安罗替尼与 Lucentis 联合治疗与 Lucentis 单药治疗相比，减少了 CNV 病变的大小和厚度。综上所述，我们的研究结果表明，安罗替尼可能是治疗眼内新生血管的一种有前途的药物候选物。
