April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Activation of Canonical Wnt Pathway Can Induce Retinopathy via Induction of ROS Generation
Author Affiliations & Notes
  • T. Zhou
    Cell Biology, Oklahoma University Health Science Center, Oklahoma City, Oklahoma
    Biochemistry, Zhongshan Medical School , Sun Yat-sen University, Guangzhou, China
  • Y. Chen
    Cell Biology, Oklahoma University Health Science Center, Oklahoma City, Oklahoma
  • Y. Hu
    Cell Biology, Oklahoma University Health Science Center, Oklahoma City, Oklahoma
  • K. K. Zhou
    Cell Biology, Oklahoma University Health Science Center, Oklahoma City, Oklahoma
  • G.-Q. Gao
    Biochemistry, Zhongshan Medical School , Sun Yat-sen University, Guangzhou, China
  • J.-X. Ma
    Cell Biology, Oklahoma University Health Science Center, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  T. Zhou, None; Y. Chen, None; Y. Hu, None; K.K. Zhou, None; G.-Q. Gao, None; J.-X. Ma, None.
  • Footnotes
    Support  NIH grants EY012231, EY015650, and P20RR024215, a grant from OCAST and a grant from ADA.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4985. doi:
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      T. Zhou, Y. Chen, Y. Hu, K. K. Zhou, G.-Q. Gao, J.-X. Ma; Activation of Canonical Wnt Pathway Can Induce Retinopathy via Induction of ROS Generation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4985.

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

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Abstract

Purpose: : The Wnt signaling pathway is known to be involved in multiple physiological and pathological processes including inflammation and angiogenesis. The purpose of this study is to investigate the role of canonical Wnt pathway in retinal inflammation.

Methods: : The Wnt3a conditioned medium and recombinant adenovirus expressing a constitutively active mutant of β-catenin (β-cateninS37A) were used to activate the Wnt pathway in cultured ARPE19 cells derived from human RPE. The accumulation of β-catenin was determined by Western blot analysis, and its nuclear translocation revealed by immunocytochemistry. The expression of inflammatory factors such as VEGF, NF-ΚB and TNF- was determined by Western blot analysis. Cellular oxidative stress was determined by measuring intracellular reactive oxygen species (ROS) generation.

Results: : The Wnt3a conditioned medium and β-cateninS37A both increased β-catenin levels and nuclear translocation in the RPE cells, suggesting activation of the canonical Wnt pathway. The activation of the Wnt pathway induced by the Wnt3A medium and by β-cateninS37A up-regulated expression of VEGF, NF-ΚB and TNF- significantly. Further, β-cateninS37A induced ROS generation in a virus titer-dependent manner, with a 4-fold increase over the control virus expressing GFP at MOI 16. Similarly, Wnt3a condition medium also induced a 2-fold increase of ROS generation in the RPE cells.

Conclusions: : Activation of the canonical Wnt pathway alone can up-regulate the expression of inflammatory factors via the induction of ROS generation. The activated Wnt pathway in diabetic retinopathy may contribute to retinal inflammation.

Keywords: neovascularization • inflammation • oxidation/oxidative or free radical damage 
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