BACKGROUND: The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease. METHODS: Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.25 mg) or 1400W (2 mg and 0.4 mg) in the left eye. Toxicity was assessed by slit-lamp and fundus examination, intraocular pressure and pachymetric measurements, and electrophysiologic and histologic analysis. RESULTS: Eyes injected with high doses of aminoguanidine (5 mg) or 1400W (2 mg) demonstrated severe retinal vascular attenuation and infarction. Lower doses of intravitreal aminoguanidine (1 mg) and 1400W (0.4 mg) caused no significant toxic ocular effects in rabbit eyes. CONCLUSION: If the difference in vitreal volume between rabbit eyes and human eyes is taken into account, aminoguanidine (2.7 mg) and 1400W (1 mg) would be reasonable intravitreal doses to test for safety and efficacy in early clinical trials.
BACKGROUND: The purpose of this study is to determine the maximum tolerated dose of a single intravitreal injection of aminoguanidine and 1400W, 2 inhibitors of inducible nitric oxide synthase, in rabbit eyes. Inhibition of inducible nitric oxide synthase has already been shown to be beneficial in various animal models of diabetic eye disease. METHODS: Groups of 4 New Zealand white rabbits were injected with balanced salt solution in the right eye and a single dose of either aminoguanidine (5, 1, 0.25 mg) or 1400W (2 mg and 0.4 mg) in the left eye. Toxicity was assessed by slit-lamp and fundus examination, intraocular pressure and pachymetric measurements, and electrophysiologic and histologic analysis. RESULTS: Eyes injected with high doses of aminoguanidine (5 mg) or 1400W (2 mg) demonstrated severe retinal vascular attenuation and infarction. Lower doses of intravitreal aminoguanidine (1 mg) and 1400W (0.4 mg) caused no significant toxic ocular effects in rabbit eyes. CONCLUSION: If the difference in vitreal volume between rabbit eyes and human eyes is taken into account, aminoguanidine (2.7 mg) and 1400W (1 mg) would be reasonable intravitreal doses to test for safety and efficacy in early clinical trials.
Authors: Roselie M H Diederen; Ellen C La Heij; Nicolaas E P Deutz; Alfons G H Kessels; Hans M H van Eijk; Fred Hendrikse Journal: Graefes Arch Clin Exp Ophthalmol Date: 2005-11-03 Impact factor: 3.117
Authors: Ana M Mueller-Buehl; Teresa Tsai; José Hurst; Carsten Theiss; Laura Peters; Lisa Hofmann; Fenja Herms; Sandra Kuehn; Sven Schnichels; Stephanie C Joachim Journal: Biology (Basel) Date: 2021-04-28
Authors: José Hurst; Ana Maria Mueller-Buehl; Lisa Hofmann; Sandra Kuehn; Fenja Herms; Sven Schnichels; Stephanie Christine Joachim Journal: J Cell Mol Med Date: 2020-03-04 Impact factor: 5.310
Authors: Jenia Kouchek Zadeh; Andreas Garcia-Bardon; Erik Kristoffer Hartmann; Norbert Pfeiffer; Wael Omran; Marion Ludwig; Andreas Patzak; Ning Xia; Huige Li; Adrian Gericke Journal: Int J Mol Sci Date: 2019-09-21 Impact factor: 5.923