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Jennifer J Kang-Mieler, Emily Dosmar, Wenqiang Liu, Sahar Hu, Kenneth M Tichauer; Novel biomarkers of diabetic retinopathy based on dynamic fluorescein enhanced fluorescent imaging. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3286a.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose was to demonstrate that the retinal vascular permeability and volumetric blood flow mapping from dynamic fluorescein enhanced fluorescent imaging can detect early changes of diabetic retinopathy (DR).
First experiment examined the changes in vascular permeability and blood flow in response to vascular endothelial growth factor (VEGF)-induced change. Under ketamine (80 mg/kg BW) and xylazine (10 mg/kg BW) anesthesia, normal animals received an intravitreal injection of VEGF (10 µg, 5 µl). A bolus of fluorescein dye (0.1 mL/kg of 10%) was injected via tail vein to obtain videoangiograms (30 sec, 20 fps, 256x256) using a Heidelberg scanning laser ophthalmoscope before the VEGF injection, and 48 hours after the injection. The fluorescein images were loaded into MATLAB and “plug flow” tracer kinetic model was applied to obtain retinal vascular permeability and blood flow maps. Second experiment examined weekly changes in control and streptozotocin (STZ, 80 mg/kg IP)-induced diabetic animals. Weekly fluorescein videoangiograms were analyzed by applying tracer kinetic model.
There was an increase in the vascular permeability (0.0061) after the VEGF injection compared to the control. The blood flow increased (31.7 ml/min/100g) after the VEGF injection compared to the control (16.9 ml/min/100g). Weekly examination of diabetic rats showed that there was an increase in the vascular permeability (0.003) as early as 2 weeks after STZ injection. There was an increase in retinal blood flow (25.6 ml/min/100g) in the diabetic rats by week 4. The diabetic rats showed high tissue blood flows where the control showed low tissue flows. Tissue blood volumes were also larger in the diabetic rats (0.290.14 ml/100g) compared to controls (0.13 0.08 ml/100g). No clinical signs of DR were observed at the time of vascular permeability and blood flow changes.
The data showed that dynamic fluorescein enhanced fluorescent imaging can detect VEGF-induced changes in normal animals. The data also demonstrated that the retinal vascular permeability changed before changes in the retinal blood flow in diabetic animals. No clinical changes of DR were observed suggesting that the vascular permeability and blood flow may be powerful biomarkers for early detection of DR.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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