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A. N. Witmer, Ocular Angiogenesis Group AMC, I. Klaassen, J. Aten, C. J. F. van Noorden, R. O. Schlingemann; Differential Expression of VEGF Receptor-2 in Retina of Diabetes Mellitus Type 1 and Type 2 Patients. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1367.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) manifests differently in type 1 and type 2 diabetes mellitus (DM1 and 2) patients, but these differences are poorly defined and unexplained. In the pathogenesis of DR, vascular endothelial growth factor (VEGF)-A signaling via VEGF receptor-2 (VEGFR2, Flk-1, KDR) in vascular and non-vascular retinal cells is crucial. In an attempt to further define differences between DR in DM1 and DM2, we investigated VEGFR2 expression in human retina with preclinical or manifest DR.
Human eyes were collected from 9 DM1 donors, 28 DM2 donors (17 on insulin) and 18 non-diabetic donors. Retinal RNA was isolated and transcription levels of VEGFR2 were measured by real-time quantitative RT-PCR analysis. Immunohistochemistry was used for comparison.
Retinal levels of VEGFR2 mRNA were found to be increased in DM1 (p=0.08) and decreased in DM2 (p=0.015), especially in retina of patients with DM2 who did not use insulin (3.5-fold, p=0.007), when compared to non-diabetic controls. Microvascular VEGFR2 protein levels were higher in DM2 as compared to controls. In both DM1 and DM2, increased VEGFR2 expression levels were found in the whole retina with manifest DR compared to preclinical DR.
Our study has identified important differences in expression levels of VEGFR2 in the human neural retina of DM1 and DM2 patients, and shows increased vascular expression during progression of DR. These differences may be relevant for understanding differences in pathogenesis of DR in both types of diabetes.
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