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D. K. Sutton, D. Martiniuk, P. Geisen, L. Peterson, Y. Saito, M. Hartnett; Intravitreous Triamcinolone Injection Significantly Increases Retinal Arterial Tortuosity in the Rat Oxygen-Induced Retinopathy Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3406.
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To determine if treatments that reduce intravitreous neovascularization (IVNV) affect retinal vascular tortuosity in the rat oxygen-induced retinopathy (OIR) model.
Newborn pups and moms were exposed to oxygen cycled between 10% and 50% every 24 hours. At postnatal day 12 (p12), pups from several litters received 1 µL intravitreous injections of neutralizing antibody to VEGF (VEGF Ab: 25 ng/µL,50 ng/µL, IgG) in one eye. Litters were returned to cycled oxygen. In remaining litters, 1 µL injections of triamcinolone (TA: 15 µg/µL, 30 µg/µL or 60 µg/µL, PBS) were given in one eye at p14. All fellow eyes were non-injected. At p14, all litters were placed into room air. At p18, retinas were flat-mounted, stained with TRITC conjugated Griffonia lectin and imaged with confocal microscopy. At least 3 retinas were analyzed for each group using vessel extraction software created at the UNC CADDLab. The course of each artery and vein was traced from its origin at the optic nerve to the image periphery. Tortuosity was calculated as a function of each vessel’s arc path. Analyses were done with ANOVA + post-hoc tests.
Eyes injected with TA had a 3-fold increase in arterial tortuosity compared to both PBS-injected and PBS non-injected eyes (p = 0.001 at 15 µg/µL, p = 0.002 at 30 µg/µL, p = 0.007 at 60 µg/µL, n = 7-9) associated with reduced clock hours of IVNV. The non-injected fellow eyes in the 30 µg/µL litter showed a 2-fold increase in tortuosity compared to controls (p = 0.026, n = 7-9) with a trend toward increased tortuosity in non-injected fellow eyes at other doses. There were no differences in arterial tortuosity in VEGF Ab treated eyes compared to control, although there was significant reduction in clock hours of IVNV. Neither drug affected venous tortuosity.
Intravitreous TA, at doses that reduce IVNV, significantly increased retinal arterial tortuosity. A crossover effect appeared in fellow eyes of TA treated pups. Intravitreous VEGF Ab, at a dose that reduces IVNV, did not affect arterial tortuosity. Since tortuosity may be associated with retinal vascular diseases and similar drugs are being considered in clinical trials, causes of increased tortuosity warrant further study.
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