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Kazuyuki Hirooka, Ye Liu, Tomoyoshi Fujita, Fumio Shiraga; Activation of the Aldosterone/Mineralocorticoid Receptor System and Protective Effects of Mineralocorticoid Receptor Antagonism in Retinal Ischemia- Reperfusion Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6409.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether the mineralocorticoid receptor (MR)-aldosterone system exists within the retina and whether it can influence retinal cell death in a rat retinal ischemia-reperfusion injury model.
Retinal ischemia was induced by increasing intraocular pressure to 130 mm Hg. Rats were treated with the angiotensin II type 1 receptor (AT1-R) antagonist (candesartan), MR antagonist (spironolactone), or aldosterone. Candesartan was administered intraperitoneally 30 min before induction of the ischemia. Aldosterone was either administered by a subcutaneous osmotic minipump 1 day before the ischemia or was injected into the vitreous space 30 min prior to the ischemia. Spironolactone was orally administered to animals on a daily basis via the use of feeding needles. At 7 days after ischemia, retinal damage was evaluated. Western blot was used to measure changes in the MR expression. Immunohistochemistry was used to examine retinal localization of MR.
Pretreatment with candesartan or 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. MR expression peaked at 12 h after ischemia, at which time the immunohistochemical analysis detected numerous MR-positive cells in the inner retina in vehicle-treated rats. Although the renin-angiotensin-aldosterone system (RAAS) was blocked by administration of candesartan, there was an increased MR expression in the inner retina at 12 h after the ischemia.
The present findings demonstrated that a local aldosterone/MR system exists in the retina. Our results also demonstrated that a MR antagonist can attenuate subsequent ischemic damage in the rat retina.
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