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

Graefes Arch Clin Exp Ophthalmol. 2015 Jan;253(1):17-23. doi: 10.1007/s00417-014-2657-8. Epub 2014 May 14.

Abstract

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 17β-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 17β-estradiol offers protection against retinal ischemic injury by inducing an upregulation in SDF-1 expression through activation of the estrogen receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / metabolism
  • Disease Models, Animal
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology*
  • Estrogen Receptor Antagonists / pharmacology
  • Estrogens / pharmacology*
  • Fulvestrant
  • Gene Expression Regulation / physiology*
  • Male
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, Estrogen / metabolism*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Retina / drug effects*
  • Retina / metabolism
  • Up-Regulation

Substances

  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Estrogen Receptor Antagonists
  • Estrogens
  • RNA, Messenger
  • Receptors, Estrogen
  • Fulvestrant
  • Estradiol