May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Aldosterone Promotes Angiogenesis and Inflammation in Ischemic Retinopathy
Author Affiliations & Notes
  • J. L. Wilkinson-Berka
    Immunology, Monash University, Prahran, Australia
  • G. Tan
    Immunology, Monash University, Prahran, Australia
  • K. Jaworski
    Immunology, Monash University, Prahran, Australia
  • A. G. Miller
    Immunology, Monash University, Prahran, Australia
  • Footnotes
    Commercial Relationships  J.L. Wilkinson-Berka, None; G. Tan, None; K. Jaworski, None; A.G. Miller, None.
  • Footnotes
    Support  Juvenile Diabetes Research Foundation International
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3875. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J. L. Wilkinson-Berka, G. Tan, K. Jaworski, A. G. Miller; Aldosterone Promotes Angiogenesis and Inflammation in Ischemic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3875.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Angiotensin II blockade is being evaluated as a treatment for diabetic retinopathy. We examined whether aldosterone, a down-stream product of angiotensin II and a potent stimulator of fibrovascular pathology, influences retinopathy of prematurity (ROP) and diabetic retinopathy.

Methods: : Bovine retinal endothelial cells (BRECs) and bovine retinal pericytes (BRPs) were cultured with aldosterone for 2 hours. ROP was induced in Sprague Dawley rats (80%/20% O2 postnatal day (P)0-11, room air P12-18). Shams were in room air. ROP groups were 1) control, 2) mineralocorticoid receptor (MR) antagonist, spironolactone (Sp, 20mg/kg/day, gavage), 3) angiotensin type 1 receptor blockade (AT1-RB, gavage), valsartan (Val, 40mg/kg/day, gavage), 4) 1% NaCl (low salt, drinking water), 5) 1% NaCl+Sp, 6) 1% NaCl+Val, 7) aldosterone (0.75microg/hr, pump), 8) aldosterone-salt, 9) aldosterone-salt+Sp and 10) aldosterone-salt+Val. Treatments were between P12-18 with 7-10 rats/group. Adult rat groups were 1) non-diabetic control, 2) streptozotocin diabetes control, 3) diabetic+MR antagonist, eplerenone (100mg/kg/day, gavage) and 4) diabetic+Val (40mg/kg/day, gavage). Rats were treated for 1 week with 9 rats/group. Blood vessels were quantitated in the inner retina (6 paraffin 3 micron sections, 60 microns apart) and leukostasis in whole retina following in vivo perfusion with ConcanavalinA. Vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1) and aldosterone synthase were measured by real-time PCR, and MR by immunohistochemistry.

Results: : MR immunolabelling was detected in neurons, glia, BRECs and BRPs. In BRECs, aldosterone induced MR translocation, proliferation and tubulogenesis. These findings translated into ROP, where aldosterone-salt was pro-angiogenic and Sp and Val, anti-angiogenic. VEGF mRNA was reduced with Val but not Sp. Leukocytes and MCP-1 are implicated in vascular remodeling in the retina. In ROP, leukostasis and MCP-1 mRNA were increased with aldosterone-salt and reduced with Sp and Val. Similarly, in diabetes, leukostasis was reduced with eplerenone and Val. Aldosterone synthase mRNA was expressed in retina and up-regulated by low salt and hyperglycaemia and down-regulated by AT1-RB and MR antagonism.

Conclusions: : To our knowledge we make the first report of a functional retinal aldosterone system and identify a previously unrecognised pathogenic role for aldosterone in ROP and diabetic retinopathy. These findings indicate that MR antagonism may be relevant when considering therapies for ischemic retinopathies which target the renin-angiotensin system.

Keywords: neovascularization • inflammation • retinopathy of prematurity 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.