June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Insulin and Angiogenesis: Excessive Insulin Induces Over-Proliferation of Tunic Vasculosa Lentis in Mice
Author Affiliations & Notes
  • Huiyi Chen
    Ophthalmology, University of Missouri-Columbia, Columbia, MO
  • Dean Hainsworth
    Ophthalmology, University of Missouri-Columbia, Columbia, MO
  • Lixing Reneker
    Ophthalmology, University of Missouri-Columbia, Columbia, MO
  • Footnotes
    Commercial Relationships Huiyi Chen, None; Dean Hainsworth, None; Lixing Reneker, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5569. doi:
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      Huiyi Chen, Dean Hainsworth, Lixing Reneker; Insulin and Angiogenesis: Excessive Insulin Induces Over-Proliferation of Tunic Vasculosa Lentis in Mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5569.

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

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Purpose: Insulin intensive treatment has been shown to slow the progression of diabetic retinopathy (DR) in many clinical trials. However, it is noticed that there is paradoxical transient worsening of DR after rapid improvement of blood glucose control with insulin treatment. The mechanism of this phenomenon is still unclear. In our lab, we observed overgrowth of tunica vasculosa lentis (TVL) in the eyes of insulin transgenic mice, suggesting that insulin may stimulate angiogenesis. The purpose of the study is to investigate the biological effects of insulin on TVL development and angiogenesis in the transgenic mouse eye.

Methods: Transgenic mice overexpressing insulin in the developing lens were generated. Abnormal development of TVL in the transgenic mouse eye was examined by histology. The vascular endothelial cells and pericytes in the TVL were identified by immunofluorescence of CD31 and NG2 respectively. The expression levels of various angiogenic factors in TVL were quantified by real-time RT-PCR and compared between the transgenic and control mice. VEGF expression pattern in TVL was analyzed by double-labeling immunofluorescence with cell type specific markers.

Results: Insulin overexpression in the lens of transgenic mice resulted in abnormal growth and delayed regression of TVL, accompanied by increase in both endothelial cells and pericytes. Endothelium-free pericyte tubes were formed in the TVL, suggesting an unbalanced angiogenic process with excess insulin stimulation. The expression levels of angiogenic factors, including VEGF, FGF-2, IGF-1, TGFβ1, TGFβ3 and PDGF-B were significantly increased in the transgenic eyes. Double-labeling immunofluorescence showed pericytes were the main sources of increased VEGF production upon insulin stimulation.

Conclusions: Insulin can act as an angiogenic stimulator during TVL development, probably by upregulating the expression of angiogenic factors such as VEGF. Our finding may provide a potential mechanism to explain the transient worsening of DR after initial intensive insulin treatment.

Keywords: 499 diabetic retinopathy • 748 vascular endothelial growth factor • 688 retina  

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