MCP-1 deficiency delays regression of pathologic retinal neovascularization in a model of ischemic retinopathy
MCP-1 deficiency delays regression of pathologic retinal neovascularization in a model of ischemic retinopathy
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DOI：
10.1167/iovs.07-1491
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Powers, Michael R.
中科院分区：
文献类型：
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作者：
Davies, Michael H.;Stempel, Andrew J.;Powers, Michael R.
目的.本研究探讨在OIR模型中MCP-1缺陷（（-/-））小鼠视网膜新生血管（NV）和细胞凋亡是否改变。出生后第7天（P）MCP-1（-/-）和C57 BL/6（B6）小鼠暴露于75%氧气5天，然后在室内空气中恢复。进行免疫染色以定位视网膜全切片和横截面内的巨噬细胞/小胶质细胞。在FITC-葡聚糖灌注的视网膜中定性评估视网膜病变，并在P17、P21和P24定量视网膜前NV。TUNEL法检测B6和MCP-1（-/-）小鼠细胞凋亡情况。MCP-1（-/-）和B6小鼠在室内空气对照中显示正常的血管发育，在P12时暴露于氧气的小鼠中显示类似的血管闭塞。与B6小鼠相比，MCP-1（-/-）小鼠表现出显著减少的血管簇相关F4/80（+）细胞。FITC-葡聚糖灌注的视网膜在P17时表现出明显的新生血管簇，并且视网膜前核的定量显示MCP 1（-/-）和B6小鼠之间没有显著差异。相比之下，在P21和P24，与B6对照组相比，MCP-1（-/-）小鼠的视网膜前新生血管核显着增加。MCP-1（-/-）小鼠NV的增加与血管丛增生的显著减少相关。结果表明，MCP-1的缺乏不会改变正常的视网膜血管发育。此外，MCP-1（-/-）小鼠在P17时表现出类似的新生血管反应。然而，MCP-1（-/-）小鼠中簇相关巨噬细胞/小胶质细胞的减少与血管簇凋亡减少和视网膜NV消退延迟相关。这些发现表明，巨噬细胞/小胶质细胞可能有助于通过其促凋亡特性的簇退化。
PURPOSE. The present study investigates whether retinal neovascularization (NV) and apoptosis are altered in MCP-1-deficient ((-/-)) mice in the OIR model.METHODS. Postnatal day (P) 7 MCP-1(-/-) and C57BL/6 (B6) mice were exposed to 75% oxygen for 5 days and then recovered in room air. Immunostaining was performed to localize macrophages/microglia within retinal whole mounts and cross-sections. Retinopathy was qualitatively assessed in FITC-dextran perfused retinas, and preretinal NV was quantified on P17, P21, and P24. TUNEL analysis was used to compare apoptosis between B6 and MCP-1(-/-) mice.RESULTS. MCP-1(-/-) and B6 mice revealed normal vascular development in room air controls and similar vaso-obliteration in oxygen-exposed mice on P12. MCP-1(-/-) mice exhibited significantly reduced vascular tuft -associated F4/80(+) cells compared with B6 mice. FITC-dextran-perfused retinas exhibited prominent neovascular tufts on P17, and quantification of preretinal nuclei revealed no significant differences between MCP1(-/-) and B6 mice. In contrast, on P21 and P24, MCP-1(-/-) mice exhibited significant increases in preretinal neovascular nuclei compared with B6 controls. These increases in NV in the MCP-1(-/-) mice were associated with a significant reduction in vascular tuft apoptosis.CONCLUSIONS. The results demonstrate that the absence of MCP-1 does not alter normal retinal vascular development. Furthermore, MCP-1(-/-)mice exhibit a similar neovascular response on P17. However, the reduction in tuft-associated macrophages/microglia in the MCP-1(-/-) mice correlates with reduced vascular tuft apoptosis and delayed regression of retinal NV. These findings suggest that macrophages/microglia may contribute to tuft regression through their proapoptotic properties.