Abstract: Objective To investigate the protective effect and mechanism of matrix metalloproteinase inhibitor-1 (TIMP-1) against diabetic retinopathy in mice. Methods A total of 96 of 6-8 weeks old C57bl mice were randomly divided into 3 groups: control group, diabetic group and TIMP-1 group (mice were intravitreously injected with TIMP-1 5μl (1μg/ml) in the first and second months respectively after diabetes-induced). Retinal vascular leakages were investigated by retinal perfusion of evans blue after 5 months. The mRNA and protein expression levels of metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α) and epoxy synthase -2 (COX-2) were also analyzed by RT-qPCR and Western blot. And the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) content in the retina tissue were also detected with bio-chemical method. Results There was no retinal leakage in control group, but diabetic group was significantly higher than TIMP-1 group (p＜0.01). The mRNA and protein expression levels of MMP-9, VEGF, TNF-α, COX-2 and the MDA content in diabetic group were significantly higher than control group (p＜0.01), while in TIMP-1 group they decreased (p＜0.01) and also higher than control group (p＜0.01). The SOD and GSH-Px activity in diabetic group were significantly lower than control group（p＜0.01),while in TIMP-1group they increased (p＜0.01) and also lower than control group (p＜0.01). Conclusions TIMP-1 can protect the retina of diabetic mice by reducing the oxidative stress and the expression of VEGF.

Key words: diabetic retinopathy, matrix metalloproteinase inhibitor-1, oxidative stress