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Ali Hafezi-Moghadam, Dawei Sun, Shintaro Nakao, Fang Xie, Souska Zandi, Zsolt Ablonczy; In Vivo Molecular Imaging Reveals Elevated VEGFR-2 Expression in Diabetic Retinal Capillaries: A Novel Biomarker for Early Diagnosis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3587.
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© ARVO (1962-2015); The Authors (2016-present)
The incidence of diabetic retinopathy (DR) is rapidly rising. Biomarkers for detection of DR are urgently needed, as vision loss can be prevented with early diagnosis and treatment. The expression dynamics of growth factors and their cognate receptors are critical in DR pathogenesis. Using our unique non-invasive molecular imaging approach, we investigate early endothelial changes in retinas of diabetic animals and introduce a novel biomarker for early detection of diabetic micro-vasculopathy.
Molecular imaging probes were custom made by conjugating carboxylated fluorescent microspheres (MSs, 2µm) with mouse IgG, anti-VEGFR-2, or VEGF. MSs (6x108) were systemically injected and their interaction in retinal vessels was studied by SLO (HRA2). Subsequently, rats were perfused with rhodamine-labeled conA and flatmounts were prepared. VEGFR-2 was quantified by Western blotting. Diabetes was induced by i.p. injection of streptozotocin in Long-Evans rats.
Our in vivo molecular imaging revealed significantly higher binding of anti-VEGFR-2 imaging probes in diabetic retinas (P=0.02), compared to normal controls. Nearly all VEGFR-2 signal was from retinal capillaries. The number of anti-VEGFR-2-Ab and VEGF molecules on our imaging probes was quantified by flow-cytometry (27453 and 27094, respectively). Western blot analysis showed significantly higher VEGFR-2 expression in diabetic retinas (P=0.04). Immunohistochemistry showed no VEGFR-2 staining in normal retinal vessels, while retinal capillaries were distinctively positive for VEGFR-2.
The present work introduces a novel biomarker for early diabetic micro-vasculopathy. The pattern and dynamics of VEGFR-2 expression in retinal capillaries might herald the progression of the disease into the proliferative stage. Our molecular imaging approach could be further developed to diagnose subclinical DR in humans.
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