Objective To investigate the protective effect of blocking the signal path of p38 mitogen activated protein kinase on blood retinal barrier (BRB) and retinal ganglion cells (RGC) in early diabetic rats.Methods A total of 60 Wistar rats were divided into the control and diabetes group, with 30 rats in each group. Diabetes was induced in rats in diabetes group by peritoneal injection of streptozotocin (STZ);the plasma glucose level of ＞16.7 mmol/L indicated that the diabetes model was set up successfully.The rats in the control group underwent peritoneal injection of equivalent sodium citrate solution. IgG leakage method was used to measure the damage of BRB function and vascular leakage. The expression and localization of caspase-3 and vascular endothelial growth factor (VEGF) in retina of diabetic rats were examined by immunohistochemistry analyses.Two weeks after the establishment of the diabtes model, the rats in diabtes group underwent intravitreal injection with SB203580, a p38 inhibitor;six weeks after the injection, the expression of caspase-3 and VEGF was detected, and the number of apoptosis RGC was counted via immunofluorescence technique.Results In the contral group, IgG staining located in the blood vessels with little leakage; while the IgG leakage was much more obvious in the diabetes group eight weeks after the establishment of the model. Six weeks after intravitreal injection with SB203580, the leakage decreased in diabtes rats. The results of semiquantitative analysis and fluorescence immunohistochemistry showed that compared with the results in diabetes rats 8 weeks after intravitreal injection (2.9 times much more than that in the control group), the fluorescence expression of VEGF decreased in diabetes rats six weeks after intravitreal injection (1.8 times much more than that in the control group).The apoptisis RGC number in rats 6 weeks after intravitreal injection of SB203580 was much less than that in rats without intravitreal injection (t＝5.731, Plt;0.01). Conclusions SB203580 can alleviate the disruption of BRB and apoptosis of RGC in early diabetes rats, which suggests that p38 MAPK pathways appear to be directly involved in the pathogenesis of early diabetic retinopathy.
Objective To quantitatively assess the damage of blood-retinal barrier (BRB) in rats with diabetic retinopathy using dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Methods Forty 3-week-old Sprague-Dawley (SD) rats were randomly divided into experiment and control group. The rats in experiment group underwent intraperitoneal injection of streptozotocin. The rats with blood glucose over 16.65 mmol/L and ldquo;+++rdquo; of urine glucose were considered as diabetes and were further divided into four subgroups according to the course of diabetes mellitus (2, 4, 6, and 8 months).The rats in control group underwent intraperitoneal injection with the same volume of buffer and were divided into four subgroups (with 5 rats in each subgroup) according to the coordinate age of rats in experimental group.All of the eyeballs were scanned by DCE MRI and enucleation was performed after intraperitoneal injection with pentobarbitone.The data were analyzed by SPSS 12.0 statistical software.Results All the rats in experiment group became diabetic models. There was no obvious BRB permeability in control group and in 2- and 4-months experiment group.The average BRB permeability rate in 6 and 8 month experiment groups were (0.1399plusmn;0.0065) and (0.1816plusmn;0.2756) mm3/min respectively (Z=-2.121, Plt;0.05). Retinal edema and cellular disorganization appeared at 4 months and became more severe when diabetes course extended.Conclusions DCE MRI can measure the BRB permeability rate accurately and assess the extent of BRB damage quantitatively in rats with diabetic retinopathy.