Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
Am J Pathol. 2010 Nov;177(5):2268-77. doi: 10.2353/ajpath.2010.100134. Epub 2010 Oct 1.
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.
基质细胞衍生因子-1(SDF-1)引起 CXCR4 表达的骨髓来源细胞的趋化作用。SDF-1 参与各种血管疾病的发病机制,包括眼部疾病。然而,SDF-1 在神经元疾病中的作用尚不完全清楚。在这里,我们发现在与正常患者相比,视网膜脱离(RD)患者的玻璃体液中 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 分析结果表明,与正常动物相比,脱离的大鼠视网膜中 SDF-1 显著上调。免疫组织化学数据显示 SDF-1 与脱离视网膜的神经胶质细胞共定位。用中和抗体阻断 SDF-1 增加了视网膜下空间中光感受器细胞的丢失和巨噬细胞的积累。视网膜前体细胞系 R28 表达 CXCR4。SDF-1 挽救了 R28 细胞因血清饥饿诱导的凋亡,并增强了它们在划痕试验中参与伤口闭合的能力。我们的结果表明 SDF-1 在 RD 中具有惊人的保护作用。这种作用可能是通过直接或间接通过其他细胞类型介导的。