17 beta -estradiol mediates upregulation of stromal cell-derived factor-1 in the retina through activation of estrogen receptor in an ischemia-reperfusion injury model

Purpose: There is increasing evidence that suggests stromal cell-derived factor-1 (SDF-1) can induce a protective response against ischemic injury in various organs. In this study, we examined the expression of SDF-1 in a rat model of retinal ischemia-reperfusion (IR) injury. Further, we explored the effect of estrogen 17 beta -estradiol (E2), and the role of estrogen receptor (ER) in regulating SDF-1 expression. Methods: Retinal IR injury was established in Sprague-Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 mins. Relative expression levels of SDF-1 mRNA and protein in the retina at 6 h, 12 h, and 24 h after reperfusion were determined by RT-PCR and western blot respectively. To investigate the influence of estrogen and ER on SDF-1 expression, E2 was administered intraperitoneally 30 mins before induction of ischemia, and the estrogen receptor antagonist ICI 182-780 was administered 1 h before E2 injection. Results: SDF-1 expression in IR-injured retina is upregulated at 6 h, 12 h, and 24 h after injury, with maximum expression at 12 h. As expected, pretreatment of retinal IR rats with E2 enhanced the upregulation in SDF-1 expression after injury, through activation of the estrogen receptor. We proved this hypothesis by demonstrating that pretreatment of retinal IR rats with ICI 182-780 led to a partial decrease in E2-induced SDF-1 expression. Conclusions: Our findings suggest that 17 beta -estradiol offers protection against retinal ischemic injury by inducing an upregulation in SDF-1 expression through activation of the estrogen receptor.