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Wenzheng Hu, Vernard Woodley, Rohn Brookes, Mike Struharik, Steve Whittaker, Steve Henry, Robin J Goody, Matthew S Lawrence; Vascular endothelial growth factor (VEGF)-induced retinal vascular leakage in African green monkeys. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2245.
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To characterize the time course of pathologic features such as retinal vascular leakage following intravitreal (IVT) injection of recombinant human VEGF165 (rhVEGF) in African green monkeys (AGMs), and to evaluate the effect of anti-VEGF therapy in reducing the pathogenic changes elicited in this model.
Eight adult male and female AGMs received repeat bilateral IVT injections of 1 or 2 µg of rhVEGF. Eyes were examined by color fundus photography, fluorescence angiography and optical coherence tomography. Lucentis 0.25 mg was administered intravitreally 2 days after the second dose of rhVEGF.
A minimum of two serial IVT rhVEGF injections were necessary to induce significant retinal vascular leakage in AGMs. Following initial dosing with 2 µg rhVEGF, the retinal appearance was similar to that observed in eyes receiving a first dose of 1 µg rhVEGF. Slight vascular dilation occurred in all eyes at day 2 with a minor retinal hemorrhage, and resolved by day 3. Two days after a second 2 µg IVT dose of rhVEGF, there was moderate dilation and tortuosity of retinal vessels, and minor vascular sheathing in the posterior retina. Changes peaked at day 3 with small patches of intra-retinal hemorrhage occurring in the posterior region. Six days after the second rhVEGF dose, moderate dilation and tortuosity of retinal vessels, and multiple intra-retinal hemorrhages were seen in both the posterior and nasal retina. Vascular dilation and tortuosity fully resolved within 11 days of the second dose. Intra-retinal hemorrhages also resolved but abundant hard exudates were deposited in the posterior retina. Lucentis-treated eyes demonstrated no fluorescein leakage in the retina although the fluorescein signal was still evident in the optic nerve head 1 day post-Lucentis treatment. No retinal vascular pathology was observed 4 days post-Lucentis injection and thereafter.
Intravitreal injections of rhVEGF produced retinal vascular leakage and other pathological changes including vascular dilation, tortuosity and sheathing, intra-retinal hemorrhage, exudates and non-perfusion regions. Pathological features were similar to those seen in diabetic retinopathy. Lucentis effectively inhibited rhVEGF-induced vascular leakage and other pathological changes, thus supporting its use as a positive control for testing anti-vascular leakage compounds in the rhVEGF model.
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