TY - JOUR
T1 - Activation of the aldosterone/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia-reperfusion injury
AU - Liu, Ye
AU - Hirooka, Kazuyuki
AU - Nishiyama, Akira
AU - Lei, Bai
AU - Nakamura, Takehiro
AU - Itano, Toshifumi
AU - Fujita, Tomoyoshi
AU - Zhang, Jinsong
AU - Shiraga, Fumio
PY - 2012/3/1
Y1 - 2012/3/1
N2 - The purpose of this project was to investigate the effects of the mineralocorticoid receptor antagonist against retinal ischemia-reperfusion injury and identify the aldosterone/mineralocorticoid receptor (MR) system in the rat retina. Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg. Rats were treated with the angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), MR antagonist (spironolactone), or aldosterone. Retinal damage was evaluated at 7 days after the ischemia by measuring the retinal thickness and the number of retinal ganglion cells. Pretreatment with candesartan, spironolactone, or candesartan and spironolactone significantly inhibited retinal ischemic injury. However, there was no protective effect against retinal ischemia-reperfusion injury provided by the combined aldosterone with candesartan treatment. Additionally, pretreatment with aldosterone alone also did not provide any neuroprotective effects against retinal ischemia-reperfusion injury. When rats were treated via local administration of aldosterone in the absence of ischemia, the number of retinal ganglion cells decreased while the retinal thickness remained unchanged. The present findings demonstrated the existence of a local aldosterone/MR system in the retina. Our results also demonstrated that an MR antagonist can attenuate subsequent ischemic damage in the rat retina.
AB - The purpose of this project was to investigate the effects of the mineralocorticoid receptor antagonist against retinal ischemia-reperfusion injury and identify the aldosterone/mineralocorticoid receptor (MR) system in the rat retina. Retinal ischemia was induced by increasing intraocular pressure to 130 mmHg. Rats were treated with the angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), MR antagonist (spironolactone), or aldosterone. Retinal damage was evaluated at 7 days after the ischemia by measuring the retinal thickness and the number of retinal ganglion cells. Pretreatment with candesartan, spironolactone, or candesartan and spironolactone significantly inhibited retinal ischemic injury. However, there was no protective effect against retinal ischemia-reperfusion injury provided by the combined aldosterone with candesartan treatment. Additionally, pretreatment with aldosterone alone also did not provide any neuroprotective effects against retinal ischemia-reperfusion injury. When rats were treated via local administration of aldosterone in the absence of ischemia, the number of retinal ganglion cells decreased while the retinal thickness remained unchanged. The present findings demonstrated the existence of a local aldosterone/MR system in the retina. Our results also demonstrated that an MR antagonist can attenuate subsequent ischemic damage in the rat retina.
KW - Aldosterone
KW - Angiotensin II type 1 receptor
KW - Mineralocorticoid receptor antagonist
KW - Retinal ischemia
UR - http://www.scopus.com/inward/record.url?scp=84857801152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857801152&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2011.12.012
DO - 10.1016/j.exer.2011.12.012
M3 - Article
C2 - 22200488
AN - SCOPUS:84857801152
VL - 96
SP - 116
EP - 123
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 1
ER -