Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-alpha and PDGFR-beta
Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-alpha and PDGFR-beta
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伊马替尼通过抑制 PDGFR-α 和 PDGFR-β 改善视网膜新生血管形成
DOI：
10.1159/000491726
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发表时间：
2018
影响因子：
--
通讯作者：
Liu Xialin
中科院分区：
文献类型：
--
作者：
Zhou Lingli;Sun Xiaowei;Huang Zijing;Zhou Tian;Zhu Xiaowei;Liu Yan;Wang Jing;Cheng Bing;Li Mei;He Chang;Liu Xialin
背景/目的血小板衍生生长因子(PDGFs)在病理性血管生成中起关键作用，是多种肿瘤和视网膜疾病的标志。在此，我们利用氧诱导视网膜病变模型评价了血小板衍生生长因子受体α和β的抑制剂伊马替尼(PDGFR-α和-β)对视网膜新生血管的抑制作用。在新生血管形成高峰期(P17)，用异凝素B4染色对新生血管面积进行定量。结果伊马替尼能有效抑制OIR小鼠病理性血管生成，减少血管内皮细胞、周细胞和平滑肌细胞的数量。此外，伊马替尼还可抑制PDGFR-α和-β的表达和激活。伊马替尼治疗的OIR小鼠表现出其他有效的促血管生成因子，如血管内皮生长因子和纤维生长因子2的表达减少。伊马替尼治疗组未见明显的视网膜或全身副作用。结论伊马替尼抑制视网膜新生血管安全有效。靶向PDGFs/PDGFRs对于抗血管生成治疗也可能是重要的，并为视网膜血管生成疾病提供一种可行的替代治疗方法。
Background/AimsPlatelet-derived growth factors (PDGFs) have emerged as pivotal in pathological angiogenesis, which is a hallmark of various tumors and retinal diseases. Here we evaluated the anti-angiogenic effect of imatinib, an inhibitor of PDGF receptors α and β (PDGFR-α and-β), in retinal neovascularization using an oxygen-induced retinopathy (OIR) model.MethodsThe OIR model was established and given imatinib or vehicle treatments daily from P12 to P16. At the peak of angiogenesis at P17, the neovascularization area was quantified on retinal whole-mounts with isolectin B4 staining. Immunofluorescence staining and western blots were used to determine the effect of imatinib on different vascular cells and the pathway molecules involved.ResultsImatinib effectively suppressed pathological angiogenesis in OIR mice and reduced the number of all three types of vascular cells, including endothelial cells, pericytes, and smooth muscle cells. Moreover, the expression and activation of PDGFR-α and-β were inhibited by imatinib. The imatinib-treated OIR mice presented with reduced expression of other potent pro-angiogenic factors such as VEGF and FGF2. No obvious retinal or systemic side effects were observed in the imatinib treatment group.ConclusionsImatinib appears to be safe and effective in suppressing retinal neovascularization. Targeting PDGFs/PDGFRs may also be important for anti-angiogenic treatment and offer a viable alternative treatment for retinal angiogenic diseases.