The retinal pigment epithelium as a gateway for monocyte trafficking into the eye
The retinal pigment epithelium as a gateway for monocyte trafficking into the eye
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DOI：
10.15252/embj.201694202
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发表时间：
2016-06-01
期刊：
影响因子：
11.4
通讯作者：
Schwartz, Michal
中科院分区：
文献类型：
--
作者：
Benhar, Inbal;Reemst, Kitty;Schwartz, Michal
在损伤条件下，包括当原发性损伤部位远离脑时，脑室内的脉络丛上皮组织协调血液来源的单核细胞进入中枢神经系统。在这里，我们假设视网膜色素上皮细胞（RPE）起到平行的作用，作为直接或远程损伤后单核细胞运输到视网膜的门户。我们发现视网膜谷氨酸中毒或视神经损伤（ONC）导致小鼠RPE中编码白细胞运输决定簇的基因表达升高。在ONC后阻断VCAM-1干扰单核细胞浸润到视网膜中，并导致局部促炎细胞因子偏倚。损伤眼的实时成像显示单核细胞首先在RPE中积聚，随后在视网膜中积聚，并且外周白细胞与RPE形成紧密接触。我们的研究结果进一步表明，眼内环境可以赋予单核细胞有利于神经保护的表型。这些结果表明，眼睛利用与大脑类似的免疫系统串扰的机制，上皮屏障作为白细胞进入的通道。
The choroid plexus epithelium within the brain ventricles orchestrates blood-derived monocyte entry to the central nervous system under injurious conditions, including when the primary injury site is remote from the brain. Here, we hypothesized that the retinal pigment epithelium (RPE) serves a parallel role, as a gateway for monocyte trafficking to the retina following direct or remote injury. We found elevated expression of genes encoding leukocyte trafficking determinants in mouse RPE as a consequence of retinal glutamate intoxication or optic nerve crush (ONC). Blocking VCAM-1 after ONC interfered with monocyte infiltration into the retina and resulted in a local pro-inflammatory cytokine bias. Live imaging of the injured eye showed monocyte accumulation first in the RPE, and subsequently in the retina, and peripheral leukocytes formed close contact with the RPE. Our findings further implied that the ocular milieu can confer monocytes a phenotype advantageous for neuroprotection. These results suggest that the eye utilizes a mechanism of crosstalk with the immune system similar to that of the brain, whereby epithelial barriers serve as gateways for leukocyte entry.