Induction of VEGF Expression in Neonatal Mice Results in Vascular Proliferation in the Inner Retina

Abstract

Abstract: : Purpose:Induction of VEGF expression in the retina of adult transgenic mice results in neovascularization in the outer retina and retinal detachment. In this study we investigated the effect of increased retinal expression of VEGF in neonatal mice. Methods:Four groups of mice were used in this study. For groups 1 and 2, litters of tetracycline inducible, human VEGF over-expressing mouse pups were transferred to nursing wild-type mothers. The mothers received 3 mg/ml of doxcycycline in their drinking water beginning on P0. Prior to sacrifice on P7, P11, P12, P13 or P16. Group 1 received no additional treatment, group 2 received a supplemental subcutaneous injection of doxycyline 1 mg/ml per gram body weight 24 hours prior to sacrifice. Groups 3 and 4 (double heterozygote, negative controls) were left with original transgenic mother and given no doxycyline water. Group 3 mice were sacrificed on same dates as listed above to serve as negative controls. Group 4 pups were injected with doxycyline on same dates and manner as group 2. Ten micron cryosections were stained with Griffonia simplicifolia lectin (endothelial cell marker) and anti-VEGF. Results:Altered inner retinal vasculature was observed in group 2 pups by P11. Inner retinal vessels located in the peripheral retina showed abnormal proliferation, dilation and tortuosity. Immunostaining for human VEGF was positive in the photoreceptor layer in group 2. Inner retinal vasculature of group 1 and 4 were normal when compared to group 3 controls. Conclusion:In contrast to adult mice, increased expression of VEGF in the retina of neonatal mice results in neovascularization and vascular dilation along the inner surface of the retina.

Keywords: 483 neovascularization • 566 retinal neovascularization • 316 animal model