Inhibitory Effect Of Angiopoietin-1 On Retinal Neovascularization Of Mice

ObjectiveAng-1 is a cytokine that specially linked to vascular endothelial cells. It is important for the angiogenesis in the embryonic period and the stability of vessels in the after birth period. To investigate the effect of angiopoietin-1 (Ang-1) on retinal neovascularization in vivo, we evaluated the relationship of Ang-1 and retinal neovascularization and the influence of Ang-1 on vascular endothelial growth factor (VEGF).MethodC57BL/6J mice were put into the environment of high oxygen to establish models of ischemic retinopathy. Thirty two mice were randomly divided into four groups: normal; control; experimental group1 (high oxygen+Ang-1, concentration: 100μg/ml); experimental group2 (high oxygen+Ang-1, concentration: 50μg/ml). The first two groups received an intravitreal injection of 1μl PBS. The other two groups received 1μl Ang-1 of different concentration. The HE straining of the retina were used to count and compare the endotheliocyte nuclei of new vessels extending from retina to vitreous in the tissue slice. Immunohistochemistry were used to evaluate the expression of VEGF. Electromicroscopy were used to evaluate the microstructure of the retina of normal group and high oxygen group.ResultThe incidence of new vessel buds in the eyes of hyperoxic group is 100%. The number of endotheliocyte nuclei of new vessels was lesser in the eyes in the experimental group1, 2 than which in the control group (p<0.01). With the increase of the concentration of Ang-1, the inhibitory effect is enhanced. Compared with the normal group, the expression of VEGF in the retina is obviously enhanced in the experimental groups and the control group. Compared with the control group, the expression of VEGF is lesser in the experimental groups (p<0.05). With the increase of the concentration of Ang-1, the expression of VEGF is lesser. Compared with the normal group, the retina of the high oxygen group is destroyed under electromicroscopy. Such as karyopykosis and vacuolar formation of mitochondria of the horizontal cells of inner nuclear layer; vacuolar formation of mitochondria of the rod and cone cells; disorder of the outer layer of the vision cells.ConclusionAng-1 can inhibit the retinal neovascularization in the eyes of the mice that breeded in the hyperoxic condition. Ang-1 can also inhibit the expression of VEGF, its effect on neovascularization may depends on its inhibitory effect on VEGF.