Characteristics of bone marrow-derived microglia in the normal and injured retina
Characteristics of bone marrow-derived microglia in the normal and injured retina
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DOI：
10.1167/iovs.08-1738
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发表时间：
2008-09-01
影响因子：
4.4
通讯作者：
Terasaki, Hiroko
中科院分区：
文献类型：
--
作者：
Kaneko, Hiroki;Nishiguchi, Koji M.;Terasaki, Hiroko
目的.比较视网膜中骨髓源性和常驻性小胶质细胞的分布和免疫学特性。对小鼠进行照射并注射增强型绿色荧光蛋白阳性（EGFP（+））BM细胞。骨髓移植后1个月至12个月，对眼睛进行组织学分析，以确定EGFP和各种单核细胞/小胶质细胞/巨噬细胞标志物（Iba-1、F4/80、GS-1、主要组织相容性复合物[MHC] II类）的表达。方法：采用N-甲基-N-亚硝基脲（N-methyl-N-nitrosourea，MNU）注射或视网膜脱离诱导视网膜损伤。在正常眼的睫状体、脉络膜和视神经周围发现了许多骨髓源性EGFP（+）细胞。骨髓移植后3 ~ 12个月，视网膜边缘和视乳头区几乎没有这种细胞存在。然而，MNU注射后，在视网膜血管、视神经和睫状体附近的视网膜中发现许多EGFP+细胞，这些细胞迅速扩散到整个视网膜。大部分肿瘤具有小胶质细胞的形态学和免疫组化特征。在注射MNU后7天，EGFP（+）BM衍生的细胞占总Iba-1（+）视网膜小胶质细胞的约15%。同时，在BM衍生的小胶质细胞（EGFP（+）/Iba-1（+））中MHC II类+细胞的比例大于驻留的小胶质细胞（EGFP（+）/Iba-1（+））。在视网膜脱离眼，EGFP（+）/F4/80（+）细胞仅在脱离的视网膜周围植入。在视网膜损伤的反应中，许多BM衍生的细胞从睫状体、视神经和视网膜血管迁移到视网膜并分化成小胶质细胞。较高的免疫激活率和对损伤部位的特异性增加似乎是BM衍生的小胶质细胞的特征性特征。
PURPOSE. To compare the distribution and immunologic characteristics of bone marrow (BM)-derived and resident microglia in the retina.METHODS. Mice were irradiated and injected with enhanced green fluorescent protein-positive (EGFP(+)) BM cells. One month to 12 months after BM transplantation, eyes were analyzed histologically for the expression of EGFP and various monocyte/microglia/macrophage markers (Iba-1, F4/80, GS-1, major histocompatibility complex [MHC] class II). N-methyl-N-nitrosourea (MNU) was injected or retinal detachment was created to induce retinal damage.RESULTS. Many BM-derived EGFP(+) cells were found in the ciliary body and choroid and around the optic nerve in the uninjured eyes. Within the retina, few such cells existed at the retinal margin and juxtapapillary area at 3 to 12 months after BM transplantation. However, after MNU injection, many EGFP+ cells were found in the retina adjacent to the retinal vessels, optic nerve, and ciliary body that rapidly spread throughout the retina. Most of them showed morphologic and immunohistochemical features of microglia. By 7 days after MNU injection, EGFP(+) BM-derived cells occupied approximately 15% of the total Iba-1(+) retinal microglia. Meanwhile, the proportion of MHC class II+ cells was larger among BM-derived (EGFP(+)/Iba-1(+)) than resident (EGFP(+)/Iba-1(+)) microglia. In the eyes with retinal detachment, EGFP(+)/F4/80(+) cells engrafted exclusively around the detached retina.CONCLUSIONS. In response to retinal damage, numerous BM-derived cells migrated to the retina from the ciliary body, optic nerve, and retinal vessels and differentiated into microglia. The higher rate of immunologic activation and the increased specificity to the damaged site appeared to be the characteristic features of BM-derived microglia.