May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
AT1R Inhibition is Retino-Protective in Retinopathy of Prematurity (ROP)
Author Affiliations & Notes
  • L. E. Downie
    The University of Melbourne, Parkville, Australia
    Optometry & Vision Sciences,
    Anatomy & Cell Biology,
  • M. J. Pianta
    The University of Melbourne, Parkville, Australia
    Optometry & Vision Sciences,
  • A. J. Vingrys
    The University of Melbourne, Parkville, Australia
    Optometry & Vision Sciences,
  • J. L. Wilkinson-Berka
    Department of Immunology, Monash University, Prahran, Australia
  • E. L. Fletcher
    The University of Melbourne, Parkville, Australia
    Anatomy & Cell Biology,
  • Footnotes
    Commercial Relationships  L.E. Downie, None; M.J. Pianta, None; A.J. Vingrys, None; J.L. Wilkinson-Berka, None; E.L. Fletcher, None.
  • Footnotes
    Support  NHMRC Grant #350434 to E. L. F. and #299974 to J. W-B. & E. L. F
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2634. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      L. E. Downie, M. J. Pianta, A. J. Vingrys, J. L. Wilkinson-Berka, E. L. Fletcher; AT1R Inhibition is Retino-Protective in Retinopathy of Prematurity (ROP). Invest. Ophthalmol. Vis. Sci. 2008;49(13):2634. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : ROP is an iatrogenic retinal neovascular disease affecting premature infants. This study has characterized the effect of angiotensin II type-1 receptor (AT1R) inhibition, using valsartan, on vascular, neuronal and glial cell pathology in experimental ROP.

Methods: : To induce ROP, newborn Sprague Dawley rats were exposed to an intermittent hyperoxic (80%:21% oxygen, 22:2 hours/day) environment until postnatal day (P) 11, then 7 days room air. Age-matched controls were raised in room air from P0-18. Valsartan (40 mg/kg/day) was administered systemically to one cohort of control and ROP pups from P12-P18; n=6-8 per group. The vascular response was examined immunocytochemically using retinal wholemounts and vertical sections labelled with endothelial (isolectin-B4) and pericyte (NG2, desmin) markers. Glial cells were assessed by measuring cell numbers and immunoreactivity (S100β, connexin-26 and glial fibrillary acidic protein). Pattern recognition analysis of multiple amino acids was used to classify retinal neural elements and quantify neurochemical disruptions in different neuronal populations.

Results: : ROP resulted in extensive intra-vitreal neovascularization and under-development of the deep vascular plexus. Pericyte numbers were not significantly affected, although pericyte-endothelial (desmin-IB4) interactions were impaired. Peripheral astrocyte degeneration occurred between P11 and P13, with prominent Müller cell gliosis at P18. The most prominent neural changes involved a loss of peripheral AII amacrine cells and a reduction of three INL neurochemical theme classes. Valsartan imparted a protective effect on all retinal elements. At P18, valsartan-treated ROP retinae showed significantly greater astrocyte survival, improved vascularization, reduced neovascularization and improved neuronal survival.

Conclusions: : AT1R-signalling blockade suppressed pathological angiogenesis and protected peripheral neurons and glia. These findings support therapeutic approaches that modulate the renin-angiotensin system in ROP.

Keywords: retinopathy of prematurity • neovascularization • glia 
×
×

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.

×