The Roles of Vitreal Macrophages and Circulating Leukocytes in Retinal Neovascularization
The Roles of Vitreal Macrophages and Circulating Leukocytes in Retinal Neovascularization
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DOI：
10.1167/iovs.10-5798
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发表时间：
2011-03-01
影响因子：
4.4
通讯作者：
Terasaki, Hiroko
中科院分区：
文献类型：
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作者：
Kataoka, Keiko;Nishiguchi, Koji M.;Terasaki, Hiroko
目的.分析玻璃体巨噬细胞和循环白细胞在视网膜血管生长中的作用。将绿色荧光蛋白（GFP）转基因小鼠的骨髓（BM）细胞移植到出生后1天（P）的小鼠体内。将小鼠暴露于76%至78%的氧气（P7-P12），以引发氧诱导的视网膜病变（OIR）。在P8、P17和P30收集眼睛，以分析视网膜中GFP阳性细胞的植入。在P5或P12时将GFP阳性腹腔巨噬细胞、氯膦酸盐脂质体或对照脂质体注射到眼中，以检查P8或P17时的作用。在P12和P17从组织切片中定量Iba 1阳性玻璃体巨噬细胞的数量。野生型和OIR小鼠在P8时视网膜中发现很少移植的GFP阳性细胞。然而，它们的数量增加，在P17在视网膜新生血管OIR。大多数GFP阳性细胞的Iba 1阳性小胶质细胞，其中包括少数的总视网膜小胶质细胞。玻璃体内注射腹腔巨噬细胞仅显示这些细胞偶然迁移到野生型视网膜中（P8），而在OIR小鼠中，通常在新血管形成周围，植入更稳健（P17）。此外，在P17时，OIR中新生血管形成期间，玻璃体腔中的天然巨噬细胞变得更少（减少37.7%）。P12时氯膦酸盐脂质体选择性清除玻璃体巨噬细胞可使OIR小鼠P17时视网膜新生血管减少59.0%。玻璃体巨噬细胞被吸引到由视网膜缺血触发的病理性血管生成部位，在那里它们积极参与血管发育。（Invest Ophthalmol维斯科学2011;52：1431-1138）DOI：10.1167/iovs.105798
PURPOSE. To analyze the roles of vitreal macrophages and circulating leukocytes in retinal vascular growth.METHODS. Bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice were transplanted into postnatal day (P)1 mice after irradiation. The mice were exposed to 76% to 78% oxygen (P7-P12), to initiate oxygen-induced retinopathy (OIR). The eyes were collected at P8, P17, and P30, to analyze the engraftment of GFP-positive cells in the retina. GFP-positive peritoneal macrophages, clodronate liposomes, or control liposomes were injected into the eyes at P5 or P12 to examine the effects at P8 or P17. The number of Iba1-positive vitreal macrophages was quantified from histologic sections at P12 and P17.RESULTS. Few transplanted GFP-positive cells were found in the retina at P8 in both wild-type and OIR mice. However, their number increased at P17 during retinal neovascularization in OIR. Most GFP-positive cells were Iba1-positive microglia, which comprised a minority of the total retinal microglia. Intravitreal injection of peritoneal macrophages showed only incidental migration of these cells into the wild-type retinas (P8), Whereas the engraftment was more robust, typically around the neovascularization, in OIR mice (P17). Furthermore, native macrophages in the vitreous cavity became fewer (37.7% reduction) during neovascularization in OIR at P17. The selective depletion of vitreal macrophages by clodronate liposomes at P12 reduced retinal neovascularization in OIR mice by 59.0% at P17.CONCLUSIONS. Vitreal macrophages are attracted to the site of pathologic angiogenesis triggered by retinal ischemia, Where they actively participate in vascular development. (Invest Ophthalmol Vis Sci 2011;52:1431-1138) DOI:10.1167/iovs.105798