April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Analysis of Myocyte Enhancer Factor 2C (MEF2C) Involvement in Retinal Vascularization in the Mouse Model of Oxygen-Induced Retinopathy
Author Affiliations & Notes
  • Zhenhua Xu
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland
  • John J. Schwarz
    Center for Cardiovascular Sciences, Albany Medical College, Albany, New York
  • Elia J. Duh
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland
  • Footnotes
    Commercial Relationships  Zhenhua Xu, None; John J. Schwarz, None; Elia J. Duh, None
  • Footnotes
    Support  NIH 1R01EY018138, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3991. doi:
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      Zhenhua Xu, John J. Schwarz, Elia J. Duh; Analysis of Myocyte Enhancer Factor 2C (MEF2C) Involvement in Retinal Vascularization in the Mouse Model of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3991.

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

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Abstract

Purpose: : MEF2C is a member of the MEF2 family of transcription factors and plays an important role in bone, muscle, and cardiovascular development. The objective of this study was to determine the role of MEF2C in normal retinal vascular development and in retinal vascularization in the oxygen-induced retinopathy (OIR) mouse model, and in retinal endothelial cells exposed to oxidative stress.

Methods: : A Tie2Cre/lox system was used to generate endothelial-specific mef2c knockout mice. Retinas from knockout mice and wild-type littermates were processed either for flat mounts or cryo-sections and stained with GS-lectin or anti-CD31 antibody for retinal vasculature analysis. CD31 and TUNEL co-immunostaining of retina was used to detect apoptotic endothelial cells under hyperoxia conditions. For the in vitro studies, human retinal endothelial cells (HREC) were transfected with MEF2C siRNA and treated with hydrogen peroxide (H2O2). The effect of MEF2C knockdown on in vitro angiogenesis was evaluated by tube formation assay. Caspase- 3/7 activity was measured to determine apoptosis. The activation of stress-related signaling pathways was also investigated using western blotting analysis.

Results: : In retinal vascular development, mef2c knockout mice displayed a similar pattern of vasculature compared with wild-type mice. In the mouse OIR model, mef2c knockout mice had significantly less avascular retina and neovascularization at P17 than wild type littermates. At P9, the avascular area was much less in knockout mice than in wild type mice. TUNEL staining showed that apoptosis of retinal endothelial cells was inhibited in mef2c knockout mice around P8. Under conditions of oxidative stress, tube formation was higher in HRECs subjected to knockdown with MEF2C siRNA compared to control siRNA. Furthermore, knocking down MEF2C in HRECs inhibited H2O2-induced apoptosis and H2O2-activated p38 MAPK signaling.

Conclusions: : Our study demonstrates that mef2c deletion in endothelial cells does not affect normal vascular development in the retina, but does alleviate vaso-obliteration and pathological neovascularization in the mouse OIR model. Both in vivo and in vitro data indicate an inhibitory role for MEF2C in endothelial cells under oxidative stress.

Keywords: retinopathy of prematurity • neovascularization • apoptosis/cell death 
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