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S. A. Frimmel, S. Zandi, S. Nakao, L. Almulki, F. Tayyari, A. Schering, A. Hafezi-Moghadam; Non-Invasive Molecular Imaging of Endothelial Injury in Diabetic Animals. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5689.
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Diabetic retinopathy (DR), a microvascular manifestation of diabetes, is a leading cause of adult vision loss.Inflammatory leukocyte recruitment constitutes one of the earliest pathological signs in experimental DR.To prevent vision loss due to structural damage, new diagnostic approaches are urgently needed. Recently, we introduced a novel molecular imaging technique for detection of endothelial injury. Here, we investigate early endothelial changes in diabetes in vivo.
Diabetes was induced by intraperitoneal injection of Streptozotocin in Long-Evans rats (180-200g). Anti Intercellular Adhesion Molecule-1 (ICAM-1) mAb, recombinant P-Selectin Glycoprotein Ligand-1 (rPSGL-1) or human IgG was conjugated to fluorescent microspheres (1-2µm diam.).Three weeks after diabetes induction conjugated microspheres were injected systemically into rats, and their adhesion in choroidal vessels was investigated under physiologic flow by scanning laser ophthalmoscopy (SLO). Subsequently, retinal and choroidal flatmounts were performed and the number of microspheres adhering to the endothelium of choroidal and retinal vessels was counted.
Microspheres conjugated with human-IgG, used as a negative control, did not show a significant difference in adhesion to the choriocapillaris between diabetic rats (9.7±1, n=5) and normal rats (10.1±1, n=6, p=0.8). A significantly higher number of rPSGL-1 conjugated microspheres adhered to the choroidal endothelium of diabetic rats (15±1, n=5), than in normal controls (8.9±0, n=5, p<0.01).Anti-ICAM-1 conjugated microspheres in diabetic rats (22.3±2, n=7) adhered to endothelium of choroidal vessels almost 3 times more compared to non-diabetic rats (8.5±1, n=8, p<0.01). Microsphere numbers in flatmounts directly corresponded to in vivo binding.In vivo, Anti-ICAM-1 conjugated microspheres adhered significantly more in diabetic rats (55±3, n=5), than in normal controls (33±2, n=5, p<0.01). In SLO adhesion of human-IgG conjugated microspheres did not show a significant difference between diabetic (24±7, n=3) and normal rats (23±5, n=3, p=0.9). In the retina only anti-ICAM-1 conjugated microspheres detected a significant difference in diabetic (16.1±2, n=10) compared to normal rats (6.4±1, n=8, p<0.01).
We introduce non-invasive detection of endothelial surface molecules in diabetes.ICAM-I provides a sensitive molecular target for detection of early changes during experimental DR.This technique could be further developed to detect subclinical signs of diabetic retinopathy in humans.
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