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L. Zheng, L. A. Levin, T. S. Kern; Endothelial Cell-Specific Overexpression of Bcl-2 Delays Neuronal and Vascular Lesions in a Retinal Ischemia/Reperfusion Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4200.
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Death of retinal cells occurs in retinal ischemia/reperfusion (I/R) and other ocular diseases, including diabetic retinopathy. The purpose of the present study is to investigate whether overexpression of Bcl-2, an anti-apoptotic protein, in the vascular endothelium could inhibit neuronal and vascular cell death in the I/R model.
Two groups of animals were used: wildtype mice (WT, C57BL/6J) and mice in whom Bcl-2 was specifically over-expressed in endothelium (Endo-bcl-2; C57BL/6J background) under the pre-proendothelin promoter. I/R injury was induced by cannulating the anterior chamber and elevating the intraocular pressure (IOP) for 90 min, and reperfusion was established immediately afterward. Density of cells in the ganglion cell layer and total retinal thickness were quantitated at 2 and 5 days after the I/R injury, and numbers of TUNEL-positive capillary cells and degenerate capillaries were assessed 8 and 14 days after the injury.
Overexpression of Bcl-2 in the endothelial cells significantly inhibited vascular cell death and capillary degeneration at 8 days after I/R injury. Vascular cell death was partially inhibited also at 14 days after the injury, but the results did not achieve statistical significance. Unexpectedly, overexpression of Bcl-2 in the endothelial cells transiently inhibited I/R-induced thinning of the retina and cell loss in the ganglion cell layer at 2 days after I/R injury.
Specific-overexpression Bcl-2 in endothelial cells delays the retinal vascular degeneration as well as neuronal degeneration in the I/R model, demonstrating a beneficial effect of preserving the vasculature on preserving neuronal integrity. Whether this is due mainly to preservation of vascular flow or to release of mediators from endothelial cells that have trophic effects on neural retina is unclear.
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