The Effect Of Intravitreal Injection Of Ranibizumab At The Early Stage Of Diabetic Retinopathy In Streptozotocin-induced Diabetic Rats

Objective:The aim of this study was to investigate the effect of Ranibizumab at a early stage of diabetic retinopathy in streptozotocin(STZ)-induced diabetic rats. Methods:DM was induced by a single intraperitoneal injection of 60 mg/kg body weight STZ. Forty diabetic rats were randomly assigned to four groups(group A: n=10, oculus dexter intravitreal injection with 1μL Ranibizumab in 2 weeks after induction; group B: n=10, oculus dexter intravitreal injection with 1μL Ranibizumab in 4 weeks after induction; group a:n=10, oculus dexter sham injections with 1μL PBS in 2 weeks after induction; group b:n=10, oculus dexter sham injections with 1μL PBS in 4 weeks after induction), while ten normal rats were assigned as group N(control, n=10, without intraocular injection). The rat retinas were obtained for flat preparation in 6 and 8 weeks after the onset of DM. Fluorescence imaging techniques for flat retinal preparations and retinal histopathological observation were used. Results:Compared with group a(10.60±0.83)or group b(11.53±0.99), there were significantly difference of retinal ganglion cells(RGCs) in group A(20.73±0.96)and group B(19.53±0.99)(P<0.01),and there was a sharp difference of IV+ collagen strands in group B by contrast to group a(14.73±1.03) or group b(14.80±0.94)(P<0.01) in 6 weeks after the onset of DM. The number of RGCs in group A(19.80±1.01) and group B(19.47±0.99) was considerably different from group a(6.67±0.90)or group b(5.80±0.94)( P<0.01), and it is considerably difference of IV+ collagen strands in group B(2.20±0.77) compared with group a(14.33±0.98) or group b(15.67±0.90)(P<0.01) in 8 weeks after induction of DM. We can also see that there is significantly difference of RGCs between group A and group B in 6 weeks after induction while it is not difference in 8 weeks. The number of RGCs in group a was different from group b at the corresponding time point in 6 weeks and 8 weeks(P<0.05), and IV+ collagen strands had not been found in group A during 8 weeks of observation period, which was obviously different from group a, b or B at the identical time point(P<0.01). Conclusion:we demonstrated that a single intravitreal injection of Ranibizumab at a very early stage of diabetic retinopathy in STZ-induced diabetic rats would induced a slow DR progression, which may be more efficacy at 2 weeks than at 4 weeks. Our results strongly suggest the study about the applicability of anti-VEGF drugs for protection against DR progression at a early stage is very important.