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S. Benac, S. Tummala, A. Appel, H. Tran, J. J. Kang Derwent; Vascular Endothelial Growth Factor (VEGF) Dependent Changes on Retinal Blood Flow in Normal and Diabetic Animal Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5905.
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The main goal of this study is to investigate retinal hemodynamic and structural changes due to VEGF level in a normal and diabetic animal model.
All measurements were performed on anesthetized adult rats. Scanning laser ophthalmoscope (SLO) was used to evaluate retinal blood velocity and diameter changes of arteries, veins, and small vessels (blood vessels <40 µm diameter). For each vessel type, an average velocity was determined by tracking 1 µm yellow-green fluorescent microspheres (505 nm maximum absorption and 515 nm maximum emission) while average diameter was measured based on infrared reflectance (IR) images. The retinal blood flow was calculated based on the cross sectional area and average velocity of the vessel. Fluoroscein angiography (FA) images were used to examine structural changes of the vessels. First set of studies investigated changes in retinal blood flow and quantification of VEGF level via ELISA assay in a normal animal injected intravitreally with 50 ng/µl (619 nmol/L vit conc) of VEGF. IR and FA images and movies were obtained at 0 hours (prior to injection) and 48 hours and 1 week post-injection. Second set of studies investigated changes in retinal blood flow and quantification of VEGF level of an animal induced with diabetes via IV injection of streptozotocin (55 mg/ml/kg, 0.1M citrate buffer). IR and FA images and movies were acquired at week 0 (prior to injection) and weekly for 8 weeks.
Significant vasodilation and tortuosity were observed in the retinal vessels 48 hours post-injection in response to VEGF injection in a normal animal. The arterial average blood flow rate and small vessel average velocity increased significantly by 48 hours post-injection. As the VEGF level decreased by week 1, blood flow rate recovered to the control level. The venous average blood flow rate showed ~11% increase by 48 hours post-injection. In diabetic animals, a significant decrease in arterial blood flow rate was observed by week 7 and significant decrease in small vessel average velocity was observed by week 6. The venous blood flow rate decreased ~13% by week 6.
Changes in blood flow rate due to alteration of VEGF level by the bolus injection of VEGF were evident in the normal eye. The blood flow rate returned to near control as the VEGF level returned to normal. The current data suggest there is a VEGF dependent change in blood flow. The diabetic animals showed significant decrease in blood flow rate by week 6.
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