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Stephen H. Poor, Chad E. Bigelow, Yubin Qiu, Shawn M. Hanks, Elizabeth Fassbender, Siyuan Shen, Amber Woolfenden, Bruce D. Jaffee; Intravitreal Ranibizumab Inhibits Injected VEGF-induced Pathology In Rabbits Up To 9 Weeks After A Single Injection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):972.
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© ARVO (1962-2015); The Authors (2016-present)
Validate a rabbit model of VEGF-mediated pathology by assessing the dose response and time course of efficacy of intravitreally injected Ranibizumab.
Ranibizumab or vehicle control in a volume of 50 µl were injected into the vitreous of Dutch belted rabbits at doses ranging from 0.6 to 500 µg. Rabbit eyes were challenged with an intravitreal injection of 400 ng of human VEGF165 (Peprotech) in saline at a volume of 50 ul at times ranging from 2 days to 9 weeks after Ranibizumab injection. Rabbit eyes were assessed 48 hours after each VEGF challenge. Assessments included measurement of retinal vascular area and leakage by scanning laser ophthalmoscopy, and ocular coherence tomography measurement of retinal structures. All images were captured with a Heidelberg Spectralis. For vessel area, rabbits were injected intravenously with 2,000 kd FITC dextran and images of the retinal blood vessels pre and post VEGF challenge were captured. Vascular leakage was assessed by intravenous injection of sodium fluorescein followed by fluorescein angiography. Fluorescein leakage was determined by subtracting the normalized dextran image from the 3-minute retinal fluorescein image.
Intravitreal injected Ranibizumab demonstrated dose dependent inhibition of VEGF-mediated vascular changes. With the VEGF165 challenge 2 days after injection of Ranibizumab, doses of 0.6 µg demonstrated partial inhibition and doses greater than or equal to 2 µg full inhibition of VEGF mediated effects. At the 5 week challenge, eyes injected with 170 and 500 µg of Ranibizumab demonstrated dose dependent inhibition and at 9 weeks 500 µg still partially inhibited VEGF-mediated changes.
Clinical doses of Ranibizumab (500 ug) are efficacious in rabbits in abrogating the effects of VEGF up to 9 weeks following a single intravitreal injection. This model system may be used to compare duration of efficacy of novel anti-VEGF agents.
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