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C. B. Westerfeld, A. Thanos, D. Vavvas, V. M. Davis, J. W. Miller, D. Milstone; E-Selectin in the Pathogenesis of Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1176.
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E-selectin is an endothelial cell-specific membrane glycoprotein that mediates leukocyte recruitment at sites of acute inflammation. E-selectin has also been demonstrated to be necessary for the anti-angiogenic activity of endostatin. Given its role in mediating inflammation and angiogenesis, we sought to study the role of E-selectin in the pathogenesis of choroidal neovascularization (CNV).
E -/- mice were generated by gene targeting. All E -/- and WT (E +/+) mice used in these experiments were obtained from matings between E +/- mice and were matched for gender, chronological age, and number of generations of sibling-cousin intercross. The mice were congenic with the mutation inbred into the C57BL/6 genetic background. Five mice from each group for a total of 20 eyes were included in the study. Four 532-nm argon laser spots (100 mW, 100 msec) were applied to each fundus using a coverslip as a contact lens. Two weeks after laser CNV induction, mice were perfused with tomato-lectin FITC (1 mg/ml) and sacrificed. CNV surface area and volume were measured using fluorescence microscopy of RPE/choroid/sclera flatmount preparations.
A thick network of new vessels was identified in the area of the laser burn. E-selectin deficient mice showed a 37.3% increase in mean CNV area (46.7 vs. 29.3 µm2; p < 0.05). E-selectin deficient mice showed a 28.7% increase in mean CNV volume (904.3 vs. 644.4 µm3; p < 0.05).
E-selectin appears to have a role in CNV formation. It is possible that in the absence of E-selectin, choroidal endothelium fails to respond to endogenous endostatin that normally limits angiogenesis and CNV formation. Additionally, the absence of E-selectin may affect leukocyte migration and inflammation that occurs in CNV. Future studies will examine these proposed mechanisms and their interaction.
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