Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human eyes and in eyes with age related macular degeneration

Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human eyes and in eyes with age related macular degeneration
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DOI:
10.1136/bjo.2006.090357
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发表时间:
2006-07-01
影响因子:
4.1
通讯作者:
Lutty, G. A.
Lutty, G. A.
中科院分区:
医学2区
文献类型:
--
作者:
Bhutto, I. A.;McLeod, D. S.;Lutty, G. A.

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目的:检测基质细胞衍生因子-1(SDF-1)及其受体CXCR4在老年对照眼和老年性黄斑变性(AMD)供眼中的免疫定位。方法:对8例老年对照供眼(平均年龄79.8岁)和12例AMD供者(平均年龄83.9岁)的身体眼进行黄斑区冷冻切片。用链霉亲和素碱性磷酸酶免疫组织化学方法定位SDF-1和CXCR4,并对切片进行漂白。结果:在老年对照视网膜中,SDF-1免疫反应在视网膜内层光感受器基质(IPM)中最强。CXCR4显示类似的免疫染色模式,但在光感受器的内节更明显。在老年对照组和AMD脉络膜中,SDF-1和CXCR4在视网膜色素上皮(RPE)细胞和脉络膜基质中的定位最为明显。然而,晚期老年性黄斑变性患者视网膜色素上皮(P<0.0001)和脉络膜基质(P<0.05)中SDF-1的表达强度显著降低。在伴有脉络膜新生血管(CNV)的盘状瘢痕中,SDF-1和CXCR4免疫反应弱或几乎不表达。结论:早期AMD患者外周血中SDF-1/CXCR4的分布及相对水平无明显变化。这提示SDF-1/CXCR4可能不参与AMD新生血管的形成,因为CXCR4+细胞不参与新生血管的形成。然而,所研究的CNV是在盘状瘢痕内,所以作者不能评论SDF-1/CXCR4在CNV形成的早期阶段中的作用。
Aim: To examine the immunolocalisation of stromal cell derived factor 1 (SDF-1) and its receptor CXCR4 in aged control human donor eyes and eyes with age related macular degeneration (AMD).Methods: Postmortem eyes from eight aged control donors (mean age 79.8 years) and from 12 donors with AMD (mean age 83.9 years) were cryopreserved and sectioned through the macular region. SDF-1 and CXCR4 were localised using streptavidin alkaline phosphatase immunohistochemistry and then sections were bleached. Three independent masked observers scored the immunohistochemical reaction product.Results: In aged control retinas, SDF-1 immunoreactivity was most intense in inner photoreceptor matrix (IPM). CXCR4 showed a similar pattern of immunostaining, but was more prominent in inner segments of photoreceptors. In aged control and AMD choroid, SDF-1 and CXCR4 localisations were most prominent in retinal pigment epithelial (RPE) cells and choroidal stroma. However, the intensity for SDF-1 was significantly reduced in RPE (p < 0.0001) and choroidal stroma (p < 0.05) in late AMD eyes. SDF-1 and CXCR4 immunoreactivities were weak or nearly absent in disciform scars with choroidal neovascularisation (CNV). Circulating cells, presumably leucocytes, were most intensely positive for CXCR4.Conclusions: These results show that changes in distribution and relative levels of SDF-1/CXCR4 were not evident in early AMD. This suggests that SDF-1/CXCR4 may not contribute to the formation of CNV in AMD, in that CXCR4+ cells were not incorporated into neovascularisation. However, the examples of CNV studied were within disciform scars, so the authors cannot comment on the role of SDF-1/CXCR4 in the early stages of CNV formation.