17β-estradiol mediates upregulation of stromal cell-derived factor-1 in the retina through activation of estrogen receptor in an ischemia-reperfusion injury model.
OBJECTIVE
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.
Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang Province, People's Republic of China, 150001.
Yeqing
Y
Wang
Xia
X
Li
Jian
J
Wang
Huanqi
H
Shi
Wenjiao
W
Bi
Wenwen
W
Hou
Xiaomei
X
Zhang
D000818:Animals; D015153:Blotting, Western; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D065171:Estrogen Receptor Antagonists; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol