Abstract
Background
Stromal cell–derived factor 1 (SDF-1) is a potent chemotactic and angiogenic factor that has been proposed to play a role in the development of neovascularization. In this study, we explored the expression of SDF-1 in a rat model of retinal ischemia-reperfusion injury and investigated the possible role of retinal microvasculature endothelium cells in generation of this chemokine.
Methods
Expression patterns of SDF-1 were studied in retina suffering ischemia-reperfusion insult in Sprague-Dawley rats by elevating the intraocular pressure to 110 mm for 60 minutes. The relative level of SDF-1 mRNA in retinas following 6, 12 and 24 hours reperfusion was determined by semi-quantitative RT-PCR. Immunohistochemical methods were used to detect specific lesions expressing SDF-1. The gene expression of SDF-1 in cultured human retinal microvasculature endothelial cells (HRMEC) under hypoxia conditions was assessed by semi-quantitative RT-PCR. The SDF-1 protein was analyzed by immunocytochemistry and fluorescence-activated cell sorting.
Results
Upregulation of SDF-1 mRNA (at 6, 12, and 24 hours of reperfusion) was observed, with the expression peak occurring at 12 hours. SDF-1 positive cells appeared initially around the retinal vessels,which diffused into the inner retinal layers. Hypoxia enhanced the expression of HIF-1 and SDF-1 mRNA in HRMEC. The production of SDF-1 protein by HRMEC was increased up to 320% after 6 hours of hypoxia, as demonstrated by fluorescence-activated cell sorting.
Conclusions
The results of our study indicate that endogenous SDF-1 is up-regulated in retinal microvasculature suffering ischemia insult, and that microvasculature endothelial cells are potential contributors for generation of SDF-1 in ischemic retina.
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Acknowledgments
This study was supported by the 5010 Project of Sun Yat-sen University in China (Grant No. 2006-45) and the Clinical Science Project of Ministry of Health in China (Grant No. 2007-353) and a scientific-technological program of Jiangxi Health department (200732020).
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We don’t have any financial relationship with the organization that sponsored the research. We have full control of all primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review these data.
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Lai, P., Li, T., Yang, J. et al. Upregulation of stromal cell–derived factor 1 (SDF-1) expression in microvasculature endothelial cells in retinal ischemia-reperfusion injury. Graefes Arch Clin Exp Ophthalmol 246, 1707–1713 (2008). https://doi.org/10.1007/s00417-008-0907-3
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DOI: https://doi.org/10.1007/s00417-008-0907-3