Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment

Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment
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DOI:
10.2353/ajpath.2010.100134
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发表时间:
2010-11-01
影响因子:
6
通讯作者:
Sakamoto, Taiji
Sakamoto, Taiji
中科院分区:
医学2区
文献类型:
--
作者:
Otsuka, Hiroki;Arimura, Noboru;Sakamoto, Taiji

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基质细胞衍生因子-1 (SDF-1)导致表达cxcr4的骨髓源性细胞趋化。SDF-1参与多种血管疾病的发病机制,包括眼睛的血管疾病。然而,SDF-1在神经元疾病中的作用尚不完全清楚。在这里,我们发现与正常患者相比,视网膜脱离(RD)患者玻璃体中的SDF-1水平更高。SDF-1与RD的持续时间和程度呈正相关。此外,SDF-1与白细胞介素-6和白细胞介素-8水平显著相关,但与血管内皮生长因子无关。Western blot分析结果显示,与正常动物相比,离体大鼠视网膜中SDF-1明显上调。免疫组化数据显示,SDF-1与离体视网膜的胶质细胞共定位。中和抗体阻断SDF-1增加视网膜下间隙光感受器细胞损失和巨噬细胞积聚。视网膜前体细胞R28表达CXCR4。在划痕实验中,SDF-1拯救了血清饥饿诱导的R28细胞凋亡,并增强了它们参与伤口愈合的能力。我们的研究结果表明,SDF-1在RD中具有令人惊讶的保护作用。这种作用可能通过其他细胞类型直接或间接介导。(中华病理学杂志,2010,177:2268-2277 DOI: 10.2353/ajpath.2010.100134)
Stromal cell-derived factor-1 (SDF-1) causes chemotaxis of CXCR4-expressing bone marrow-derived cells. SDF-1 is involved in the pathogenesis of various vascular diseases, including those of the eye. However, the role of SDF-1 in neuronal diseases is not completely understood. Here, we show higher SDF-1 levels in the vitreous humor of patients with retinal detachment (RD) compared with normal patients. SDF-1 correlated positively with the duration as well as the extent of RD. Furthermore, SDF-1 correlated significantly with levels of interleukin-6 and interleukin-8, but not with vascular endothelial growth factor. Western blot analysis results showed significant SDF-1 up-regulation in detached rat retinas compared with normal animals Immunohistochemistry data showed that SDF-1 was co-localized with the glial cells of the detached retina. SDF-1 blockade with a neutralizing antibody increased photoreceptor cell loss and macrophage accumulation in the subretinal space. The retinal precursor cell line R28 expressed CXCR4. SDF-1 rescued serum starvation-induced apoptosis in R28 cells and enhanced their ability to participate in wound closure in a scratch assay. Our results indicate a surprising, protective role for SDF-1 in RD. This effect may be mediated directly or indirectly through other cell types. (Am J Pathol 2010, 177:2268-2277 DOI: 10.2353/ajpath.2010.100134)