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D. J. Martiniuk, Z. Zhao, D. K. Wallace, M. E. Hartnett; Reducing the Bioactivity of VEGF With a Neutralizing Antibody Significantly Reduces Arteriole Tortuosity in a Rat Model of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1409.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate retinal vascular tortuosity, a major component of plus disease in human retinopathy of prematurity (ROP), in a rat model.
Newborn Sprague-Dawley rats and their mothers were placed in an Oxycycler (Biospherix, NY), which cycled oxygen between 10 and 50% every 24 hours for 14 days. Pups within litters were removed from the Oxycycler and at postnatal day (p)12 , were given one µL intravitreous injections of: 50 ng of a neutralizing antibody made against vascular endothelial growth factor (VEGF)164 or IgG control; or 10 µM SU5416, a non-specific VEGF receptor 2 inhibitor, or DMSO control. We had previously found these doses to significantly reduce intravitreous neovascularization in the model at p18. Tortuosity of the major vessels using ROPtool v. 1.1(UNC Department of Radiology’s CADDLab) was determined from TRITC conjugated Griffonia isolectin-stained flat mounts of retinas from pups from the 50/10 OIR or room air raised controls at p11, p12, p14, and p18.
Rats in the 50/10 OIR model had increasing arteriolar tortuosity over time (compare p11 vs. p12 and p14; ANOVA < 0.001) and compared to room air raised controls. Neutralizing antibody to VEGF164 significantly reduced arteriolar tortuosity compared to IgG control (ANOVA < 0.004) and untreated fellow eyes (ANOVA < 0.049) at p14. Injection of 10 µM SU5416 had no significant effect on arteriole or venous tortuosity at p14.
In the 50/10 OIR model, arteriolar tortuosity increased at p12 and remained elevated through p18. This observation occurred prior to the development of intravitreous neovascularization that occurs at p18. Furthermore, inhibition of the bioactivity of VEGF using a neutralizing antibody, but not a non-specific VEGF receptor 2 inhibitor, was associated with reduced tortuosity of arterioles.
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