April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Aldosterone Induces Apoptosis in Human Retinal Pigment Epithelium
Author Affiliations & Notes
  • Dongli Yang
    Ophthal & Vis Sci, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • Susan G. Elner
    Ophthal & Vis Sci, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
  • Victor M. Elner
    Ophthal & Vis Sci, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, Michigan
    Pathology, University of Michigan, Ann Arbor, Michigan
  • Footnotes
    Commercial Relationships  Dongli Yang, None; Susan G. Elner, None; Victor M. Elner, None
  • Footnotes
    Support  NIH grants EY09441 (V.M. Elner) and P30EY07003 (core). VME is a recipient of Lew R. Wasserman Merit Award from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 862. doi:
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      Dongli Yang, Susan G. Elner, Victor M. Elner; Aldosterone Induces Apoptosis in Human Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2011;52(14):862.

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Abstract

Purpose: : Age-related macular degeneration (AMD) is the leading cause of legal blindness among the elderly in the United States. Principal risk factors for AMD are age, race, smoking, and cardiovascular disease, but its cause remains unknown. A key mechanistic element in the progression of AMD is dysfunction and apoptotic loss of the retinal pigment epithelium (RPE). Aldosterone has attracted considerable attention for its involvement in the pathogenesis of cardiovascular disease. Epidemiological studies show that many of risk factors for AMD also represent a cardiovascular risk profile, suggesting that AMD and cardiovascular disease may have similar etiological mechanisms. The purpose of this study was to determine whether aldosterone directly induces RPE apoptosis and whether aldosterone-induced RPE apoptosis is mediated by mineralocorticoid receptors (MR).

Methods: : Human RPE cell cultures were used. Apoptosis was evaluated by Hoechst staining, in situ detection of activated caspases, caspase-3, and annexin-V staining.

Results: : Cultured human RPE cells were exposed to 0-100 nM aldosterone for 48 hr. Compared to control RPE cells, aldosterone increased the numbers of apoptotic cells, as indicated by Hoechst 33342 staining of distinctive, irregular apototic nuclei, in a dose-dependent manner. Aldosterone-induced RPE apoptosis was confirmed by in situ detection of activated caspases, caspase-3, and annexin-V staining. RPE pretreatment with the MR antagonist, spironolactone (20 µM) significantly reduced aldosterone-induced apoptosis.

Conclusions: : This is the first evidence that aldosterone induces RPE apoptosis. The data indicate that aldosterone-induced apoptosis is mediated through MR-dependent pathway. These findings suggest that currently available anti-aldosterone drugs may be useful in the treatment of AMD and that new therapies involving the aldosterone pathway may be applicable to AMD.

Keywords: retinal pigment epithelium • apoptosis/cell death • age-related macular degeneration 
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