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FASEB J. 2014 Sep;28(9):3942-51. doi: 10.1096/fj.14-251934. Epub 2014 Jun 5.

Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

Author information

1
Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Radiology and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; Department of Ophthalmology, Second Affiliated Hospital of Harbin Medical University, Harbin, China;
2
Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Radiology and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA;
3
Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
4
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran;
5
National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; and.
6
Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Radiology and.
7
Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA.
8
Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Radiology and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA; ahm@bwh.harvard.edu.

Abstract

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients.

KEYWORDS:

endothelial injury; preventive care; probe development; retinopathy

PMID:
24903276
PMCID:
PMC4139900
DOI:
10.1096/fj.14-251934
[Indexed for MEDLINE]
Free PMC Article
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