Aim
To clarify the mechanism of infliximab treatment in diabetic macular edema (DME) and to provide a new alternative therapy for DME.
Conclusion
In a diabetic rat model, infliximab may relieve TNF-α induced BRB breakdown via the B-Raf and p38 signaling pathway.
Methods
Rats were randomly divided into the control group, the model group and the infliximab treatment group. A diabetic rat model was created. The concentration of TNF-α in the vitreous body was detected by ELISA. The expressions of B-Raf, p38, claudin-1 and occludin in the retina were detected by Western blot. The integrity of the blood retinal barrier (BRB) was measured using Evan's blue as a tracer.
Results
After three months and six months of the diabetes model, the vitreous TNF-α level in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant (at 3mo, F=857.098, P<0.001; 6mo, F=1261.897, P<0.001). The retina B-Raf and p38 levels in the model group were higher than that of the control group. They were also higher in treated group than that of the control group but were lower than that of the model group. The differences among the three groups were statistically significant (B-Raf at 3mo, F=106.596, P<0.001 and at 6mo, F=200.681, P<0.001; p38 at 3mo, F=41.662, P<0.001 and at 6mo, F=67.979, P<0.001). The retina claudin-1 and occludin levels in the model group were lower than that of the control group. They were also lower in treated group than that of the control group but were higher than that of the model group. The differences among three groups were statistically significant (claudin-1 at 3mo, F=139.088, P<0.001 and at 6mo, F=128.415, P<0.001; occludin at 3mo, F=92.733, P<0.001 and at 6mo, F=104.478, P<0.001). The retinal Evans blue leakage in the model group was higher than that of the control group. It was also higher in treated group than that of the control group but was lower than that of the model group. The differences among the three groups were statistically significant (at 3mo, F=447.946, P<0.001; at 6mo, F=1610.732, P<0.001).