Objective To elevate the effect of intravitreal Bevacizumab injection on the repair of BRB and prevention diabetic macular edema and retina neovascularization,to prove that it can reduce the progression of DR.
Method There was totally 80 healthy Sprague Dawley rats in which 13 rats were chosen as normal group and 67 rats were constructed for diabetic model by streptozotocin (STZ). Evans blue(EB) angiography and flash-electroretinogram (FERG) were used to ensure that the diabetic rats had nonproliferative diabetic retinopathy(NPDR) in the 10th week after successful model making. The diabetic model were divided into three groups randomly including control model group (DR group) ,high-dose treatment group(H group) and Low-dose treatment group(L group).After that, Bevacizumab were injected into the vitreous in the treatment group ,the dose was 2.5mg/ml×4μl and 1.25 mg/ml×4μl ,respectively. Nothing was injected into DR group and normal group.2 weeks、4weeks、6weeks after injection, the rats were executed and eyes were enucleated. The expression of VEGF in retinas was assessed by Immunohistochemistry assay . EB perfusion method were used to assess the function of BRB. EB angiography was used to assess the capillary vessel pattern after Bevacizumab injection.
Result VEGF was mainly weakly expressed in the retina inner nuclear layer and nerve fiber layer cytoplasm, the color is pale yellow in N group. VEGF levels were expressed in all layers of the retina, but mainly in the nerve fiber layer, inner nuclear layer and inner limiting membrane, the expression is stronger than N group and the color is brown in DR group. VEGF levels were expressed mainly in the nerve fiber layer and inner nuclear layer in teatment group,but the expression is weaker than DR group while stronger than N group. EB perfusion method:2 weeks after the treatment, EB leakage of treatment groups were lower than DR group and higher than N group（P=0.000）,there were were no statistically significant differences between the H group and L group（P=0.364）;4 weeks after the treatment, EB leakage of treatment groups were lower than DR group and higher than N group（P=0.000）, there were statistically significant differences between the H group and L group（P=0.035）; 8 weeks after the treatment, EB leakage of treatment groups were lower than DR group and higher than N group（P=0.000）, there were statistically significant differences between the treatment group（P=0.031）. EB angiography: DR group:2 weeks after the treatment, the density of microvascular increase; vessels run tortuous; EB leaked from the branch of retinal vessels，some microaneurysms is visible but neovascularization is unvisible. 4 and 8 weeks after the treatment, retinal vascular irregularly expanded and run tortuosity; there were microaneurysms and no perfusion zone; there was large-scale EB leakage in the peripheral retina. Retinal vascular density was significantly higher than the N group and lower than DR group; retinal vascular tortuosity was not obvious, and no dye leakage, and no microaneurysms and no-perfusion zone in treatment group; Occasionally , there were retina vascular leakage in L group, but no in H group.
Conclusion Intravitreal injection of Bevacizumab is effective in preventing rats diabetic macular edema and DR retinal neovascularization, it is possible to delay the occurrence of proliferative DR. The effet of Intravitreal Bevacizumab injection is dose-related, at least 8 weeks, the effect is stable .
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