Angiostatic Effect of CXCR3 Expressed on Choroidal Neovascularization
Angiostatic Effect of CXCR3 Expressed on Choroidal Neovascularization
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DOI：
10.1167/iovs.11-8232
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发表时间：
2012-04-01
影响因子：
4.4
通讯作者：
Yanagi, Yasuo
中科院分区：
文献类型：
--
作者：
Fujimura, Shigeto;Takahashi, Hidenori;Yanagi, Yasuo
目的.最近的一些研究表明，一些趋化因子/趋化因子受体参与脉络膜新生血管（CNV）。CXCR 3是本研究的重点，因为微阵列分析小鼠激光诱导的CNV模型显示CXCR 3的表达增加。本研究的目的是评价CXCR 3在CNV中的作用。对激光诱导的CNV小鼠眼进行微阵列分析。免疫组化和实时荧光定量PCR检测CNV中CXCR 3的表达。在CXCR 3缺陷型小鼠和野生型小鼠之间、在用抗CXCR 3/抗IP 10中和抗体处理的小鼠和用对照IgG处理的小鼠之间比较CNV。还研究了巨噬细胞募集到CNV中。通过实时荧光定量PCR评估血管内皮生长因子（VEGF）、色素上皮衍生因子（PEDF）、C-C趋化因子配体-2（CCL 2）和补体成分-3（C3）的眼部表达。微阵列分析和实时RT-PCR显示，与对照眼相比，激光处理的小鼠眼中CXCR 3和IP-10升高。免疫组化显示CNV内皮细胞CXCR 3表达。与野生型小鼠相比，CXCR 3缺陷型小鼠的激光诱导的CNV显著更大，荧光素血管造影中的渗漏更大，并且具有更大的巨噬细胞浸润（P < 0.01）。玻璃体内注射抗CXCR 3/抗IP-10中和抗体加重CNV。CXCR 3基因缺陷小鼠激光治疗眼的CCL 2表达高于野生型小鼠（P <0. 05），而VEGF、PEDF和C3表达无差异。这些结果表明在CNV上表达的CXCR 3可以对其具有血管抑制作用。2012;53：1999-2006）DOI：10.1167/iovs.11-8232
PURPOSE. Several recent studies suggest that some chemokines/chemokine receptors are involved in choroidal neovascularization (CNV). CXCR3 was the focus of the present study because microarray analysis for murine laser-induced CNV model showed the increased expression of CXCR3. The purpose of this study was to evaluate the effect of CXCR3 on CNV.METHODS. Microarray analysis was performed for the mouse eyes with laser-induced CNV. CXCR3 expressions on the CNV were evaluated by immunohistochemistry and real-time RT-PCR. CNV was compared between CXCR3-deficient mice and wild-type mice, between mice treated with anti-CXCR3/anti-IP10 neutralizing antibody and mice treated with control IgG. Macrophage recruitment into CNV was also investigated. Ocular expressions of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), C-C chemokine ligand-2 (CCL2), and complement component-3 (C3) were evaluated by real-time PCR.RESULTS. Microarray analysis and real-time RT-PCR revealed the elevation of CXCR3 and IP-10 in laser-treated mouse eyes compared with control eyes. Immunohistochemistry showed CXCR3 expression on the endothelial cells of CNV. Laser-induced CNV of CXCR3-deficient mice was significantly larger, with greater leakage in fluorescein angiography, and with greater macrophage-infiltration compared with wild-type mice (P < 0.01). Intravitreal injection of anti-CXCR3/anti-IP-10 neutralizing antibody exacerbated CNV. The CCL2 expression in the laser-treated eyes of CXCR3-deficient mice was higher than in those of wild-type mice (P < 0.05), whereas VEGF, PEDF, and C3 showed no differences.CONCLUSIONS. These results suggested that CXCR3 expressed on CNV could have an angiostatic effect on it. (Invest Ophthalmol Vis Sci. 2012;53:1999-2006) DOI:10.1167/iovs.11-8232