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Activation of the aldosterone/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia-reperfusion injury.

Abstract

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.

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  • Publisher Full Text
  • Authors

    Liu Y, Hirooka K, Nishiyama A, Lei B, Nakamura T, Itano T, Fujita T, Zhang J, Shiraga F

    Source

    Experimental eye research 96:1 2012 Mar pg 116-23

    MeSH

    Aldosterone
    Angiotensin II Type 1 Receptor Blockers
    Animals
    Benzimidazoles
    Cell Survival
    Male
    Mineralocorticoid Receptor Antagonists
    Rats
    Rats, Sprague-Dawley
    Renin-Angiotensin System
    Reperfusion Injury
    Retinal Diseases
    Spironolactone
    Tetrazoles

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22200488