May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Bcl-2, Endothelial Death, and Capillary Degeneration in Diabetic Retinopathy
Author Affiliations & Notes
  • T. S. Kern
    Case Western Reserve Univ, Cleveland, Ohio
    Department of Medicine and Ophthalmology,
  • Y. Du
    Case Western Reserve Univ, Cleveland, Ohio
    Department of Medicine,
  • L. A. Levin
    Department of Ophthalmology and Visual Science, University of Wisconsin, Madison, Wisconsin
  • Footnotes
    Commercial Relationships T.S. Kern, None; Y. Du, None; L.A. Levin, None.
  • Footnotes
    Support EY00300
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3638. doi:
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      T. S. Kern, Y. Du, L. A. Levin; Bcl-2, Endothelial Death, and Capillary Degeneration in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3638.

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

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Purpose:: Apoptosis is believed to be a crucial step in the development of diabetic retinopathy, and Bcl-2 has been found to regulate cellular susceptibility to apoptosis. We studied (1) the effect of diabetes and hyperglycemia on expression of Bcl-2 in retina and retinal endothelial cells, (2) the ability of Bcl-2 to inhibit hyperglycemia-induced death of retinal endothelial cells and degeneration of retinal capillaries in diabetes, and (3) the roles of nitric oxide, cyclooxygenase-2 (COX-2) and caspases on hyperglycemia-induced alterations in Bcl-2 expression.

Methods:: Nondiabetic and diabetic wildtype mice and transgenic mice overexpressing Bcl-2 selectively in endothelium (using the preproendothelin promoter) were used. For in vitro experiments, primary bovine retinal endothelial cells (BREC) were incubated in 5mM and 25 mM glucose.

Results:: In vivo, diabetes decreased Bcl-2 expression in whole retina, increased the rate of endothelial cell death in retinal capillaries, and caused degeneration of retinal capillaries (resulting in acellular capillaries). Diabetes-induced degeneration of retinal capillaries over an 8 month period was inhibited in animals overexpressing Bcl-2 in the endothelium. In vitro findings were consistent with the in vivo studies. Elevated glucose decreased Bcl-2 expression in BREC, and death of BREC in elevated glucose was significantly inhibited by incubating the cells with a peptide containing a cell-permeable, BH4 (anti-apoptotic) domain of Bcl-2. Inhibition of NO production (with L-NAME), COX-2 (with NS-398), or caspases (with BD-FMK) inhibited the decrease in Bcl-2 and increase in cell death due to elevated glucose in vitro.

Conclusions:: Diabetes-induced increase in retinal capillary cell death can be inhibited by over-expression of the anti-apoptotic protein Bcl-2. We postulate that Bcl-2 downregulation contributes to the process of retinal vascular cell death and development of retinopathy in diabetes, and that therapies that preserve Bcl-2 will help inhibit the development of diabetic retinopathy.

Keywords: apoptosis/cell death • diabetic retinopathy 

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