title: Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.
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.
authors.affiliation: 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;
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.affiliation: 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;
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.affiliation: 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;
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: 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;
authors.forename: Souska
authors.initials: S
authors.lastname: Zandi
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
authors.forename: Abouzar
authors.initials: A
authors.lastname: Bagheri
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
authors.forename: Mozhgan Rezaei
authors.initials: MR
authors.lastname: Kanavi
authors.affiliation: Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran;
authors.forename: Shahram
authors.initials: S
authors.lastname: Samiei
authors.affiliation: National Institute of Genetic Engineering and Biotechnology, Tehran, Iran; and.
authors.forename: Zahra-Soheila
authors.initials: ZS
authors.lastname: Soheili
authors.affiliation: 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;
authors.forename: Sonja
authors.initials: S
authors.lastname: Frimmel
authors.affiliation: Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Radiology and.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Ablonczy
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.affiliation: 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.
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D002196:Capillaries / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D020318:Rats, Long-Evans; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: endothelial injury; preventive care; probe development; retinopathy