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G. G. Gum, R. A. P. de Carvalho, P. M. Evans; Matrigel-Based Models of Retinal and Choroidal Neovascularization in Rabbits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):537.
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To develop a model of retinal and choroidal neovascularization in rabbits and to characterize the effects of intravitreal and subretinal injections of Matrigel carrying angiogenic growth factors on the retinal and choroidal vasculatures.
Dutch Belt (n = 9) and White New Zealand rabbits (n = 12) were injected with Matrigel containing no growth factors (control), or a mixture of Matrigel and basic fibroblast growth factor (bFGF). An additional group had the combination of vascular endothelial growth factor (VEGF) and bFGF added to the Matrigel. To mimic retinal neovascularization and choroidal neovascularization, the intravitreal and subretinal injection routes were utilized respectively. Fluorescein angiography demonstrated in vivo the choroidal and retinal vascular changes. Grading of fluorescein angiography images followed qualitative and quantitative clinical standards, where lesions where graded according to type, size and severity. Animals were followed for 4 weeks or longer, when indicated.
Intravitreal injection of Matrigel without growth factors led to a mild to moderate vitreal inflammation that progressed up to week 2, and with signs suggestive of posterior vitreous detachment and mild retinal traction along the vascular arcades. Vascular dilation association with bFGF was observed in retinal and iris vessels as soon as day 4. The inflammation was still present, however, retinal vascular dilation followed by increased tortuosity and hyperfluorescence, suggestive of retinal neovacularization, were observed at week 2 and progressed to tractional retinal detachment at week 4.Subretinal injection led to transient retinal vascular ischemic changes in Matrigel-only injected eyes, but severe and sustained ischemic changes were observed when growth factors were added to the Matrigel. Diffuse hyperfluorescence due to exsudation into the subretinal space persisted up to week 4.
Matrigel in combination with angiogenic growth factors can trigger a retinal or choroidal neovascular response after intravitreal or subretinal injection in rabbits. This can offer the opportunity for testing drugs that interfere with the angiogenic cascade. Further studies utilizing approved anti-angiogenic drugs are warranted to validate this as a combined pharmacokinetic and pharmacodynamic model of retinal and choroidal neovascular diseases.
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