April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
RAGE-S100B Ligand Interactions Play An Important Regulatory Role In Angiogenesis Invitro And Choroidal Neovascularization (CNV) Invivo
Author Affiliations & Notes
  • Shilpa Dasari
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Josephine V. Glenn
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Mei Chen
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Liza Colhoun
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Michael Quinn
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Heping Xu
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Angelika Bierhaus
    Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany
  • Alan W. Stitt
    Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, United Kingdom
  • Footnotes
    Commercial Relationships  Shilpa Dasari, None; Josephine V. Glenn, None; Mei Chen, None; Liza Colhoun, None; Michael Quinn, None; Heping Xu, None; Angelika Bierhaus, None; Alan W. Stitt, None
  • Footnotes
    Support  Fight For Sight
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 1801. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shilpa Dasari, Josephine V. Glenn, Mei Chen, Liza Colhoun, Michael Quinn, Heping Xu, Angelika Bierhaus, Alan W. Stitt; RAGE-S100B Ligand Interactions Play An Important Regulatory Role In Angiogenesis Invitro And Choroidal Neovascularization (CNV) Invivo. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1801.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : The receptor for AGEs (RAGE) binds to a range of ligands to evoke pro-inflammatory signaling responses in diverse cells and tissues. This study has investigated how RAGE and its ligands modulate key processes that lead to CNV.

Methods: : C57Bl/6 control (WT) and RAGE null (RAGE-/-) mice, (12 wks, n=12/group) underwent diode laser photocoagulation to generate CNV lesions. Fundus photography and cSLO images of Indocyanine green angiography were used to evaluate lesions. Post-mortem, eyes were enucleated 7 days post laser exposure and retinal flat-mounts analyzed for CNV lesion morphology, occurrence of the RAGE-ligand S100B and inflammatory cell infiltration. In a parallel in vitro study with human endothelial cells (HMEC-1), the angiogenic response (cell migration and tubulogenesis in Matrigel®) of S100B was assessed. siRNA was then used to knockdown RAGE expression in HMEC-1 and S100B-mediated angiogenesis, NFΚB transcription and PI3K / Akt phosphorylation were analyzed.

Results: : Retina from RAGE -/- mice exhibited significantly reduced CNV lesion size when compared to WT controls (p<0.05) (n=12/group). Activated microglia were considerably less abundant in CNV lesions from RAGE-/- mice when compared to WT counterparts (p<0.001). S100B immunostaining was high around the CNV lesions of WT mice when compared to those in RAGE-/- mice. S100B-treated HMEC-1 cells showed increased migration and tube formation (p<0.001) phosphorylation of the Akt (PI3K) pathways and subsequent NFΚB transcriptional activation. siRNA mediated knockdown of RAGE significantly prevented all these HMEC-1 responses to S100B.

Conclusions: : RAGE plays an important role in CNV lesion formation. Pro-inflammatory and angiogenic responses appear to be mediated by S100B-RAGE interactions. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology.

Keywords: age-related macular degeneration • laser • choroid: neovascularization 
×
×

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.

×