Sun Dawei, Nakao Shintaro, Xie Fang, Zandi Souska, Bagheri Abouzar, Kanavi Mozhgan Rezaei, Samiei Shahram, Soheili Zahra-Soheila, Frimmel Sonja, Zhang Zhongyu, Ablonczy Zsolt, Ahmadieh Hamid, Hafezi-Moghadam Ali
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;
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;
FASEB J. 2014 Sep;28(9):3942-51. doi: 10.1096/fj.14-251934. Epub 2014 Jun 5.
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.
糖尿病视网膜病变（DR）是糖尿病的一种微血管并发症，也是视力丧失的主要原因。迫切需要用于DR早期诊断的生物标志物和方法。使用一种新的分子成像方法，我们发现，与正常对照组相比，针对血管内皮生长因子受体2（VEGFR-2）定制设计的成像探针在糖尿病动物的视网膜和脉络膜血管中的积累量高达94%（P<0.01）。糖尿病视网膜中超过80%的VEGFR-2存在于毛细血管中，而正常对照组中这一比例为47%（P<0.01）。兔视网膜血管造影显示，微血管毛细血管是VEGF-A诱导渗漏的部位，与注射赋形剂对照组相比，注射VEGF-A时荧光团扩散速率显著更高（26±2对3±1μm/s，P<0.05）。免疫组织化学显示VEGFR-2在糖尿病动物的毛细血管中表达，但在正常对照组中不表达。与非糖尿病对照组（n=5）或同一视网膜的周边视网膜区域相比，糖尿病患者（n=7）的黄斑血管显示出显著更多的VEGFR-2（两种情况下P均<0.01）。在此，我们介绍一种DR早期诊断的新方法以及将VEGFR-2作为分子标志物。VEGFR-2可能成为一个关键的诊断靶点，有助于预防糖尿病患者视网膜血管渗漏和增殖。
