Effect of FTY720 on retinal leukocytes adhesion and vascular permeability in diabetic rats / 中华眼底病杂志

ABSTRACT

Objective To evaluate the effect of FTY720 on retinal leukocytes adhesion and vascular permeability in diabetic retinopathy (DR) model,and explore its mechanism.Methods Ninety male Wister rats were randomly divided into normal control group,diabetic group and FTY720 group,thirty rats in each group.Diabetes was induced by giving a single intraperitoneal injection of streptozocin.FTY720 group was administered with FTY720 at a dose of 0.3 mg/kg by oral gavage daily for 3 months after establishment of diabetes.All rats were used for experiments following intervention for 3 months in FTY720 group.Immunohistochemical staining was used to observe the expression and distribution of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1),and the positive cells were counted.Real-time reverse transcription PCR was used to measure mRNA expression of ICAM-1 and VCAM-1.Fluorescein isothiocyanate-Concanavalin A perfusion was used to detect retinal leukocytes adhesion.Evans blue (EB) perfusion was used to analyze retinal vascular permeability.Immunofluorescence staining was used to detect retinal inflammatory cells infiltration.Results In diabetic group,both ICAM-1(t =12.81) and VCAM-1 (t=11.75) positive cells as well as their mRNA expression (t=16.14,9.59) were increased compared with normal control group,with statistical significance (P＜ 0.05).In FTY720 group,both ICAM-1(t=-9.93) and VCAM-1 (t=-6.61) positive cells as well as their mRNA expression (t=-15.28,-6.10) were decreased compared with diabetic group,with statistical significance (P＜ 0.05).Retinal leukocytes adhesion (t=16.32) and EB permeability (t=17.83) were increased in diabetic group compared with normal control group,while they were decreased in FTY720 group compared with diabetic group(t=-9.93,-11.82),with statistical significance (P＜0.05).There were many CD45 positive leukocytes infiltration in retina of diabetic group,including CD11b positive macrophage/activated microglia,while both of them were little in FTY720 group.Conclusions FTY720 can decrease retinal leukocytes adhesion,reduce retinal vascular permeability and inflammatory cells infiltration,which is associated with down-regulation of ICAM-1 and VCAM-1.