A pilot study on phosphorylation of extracellular signal-regulated kinase 1/2-mediated diabetic retinopathy / 中华实验眼科杂志

ABSTRACT

Background It is well known that diabetic retinopathy(DR) involves in complex pathogenesis.Worse outcome of brain ischemia with hyperglycemia is mediated by mitogen-activated protein kinases (MAPK).However,the effect of phosphorylation of MAPK signal pathway on DR needs further investigation.Objective This study was to explore the the possible role of extracellular signal-regulated kinase1/2(ERK1/2)in DR.Methods Sixty SPF SD rats aged 8-weeks were grouped into the control group and diabetes group.Diabetic models were established by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) dissolved in citric acid buffer.Blood glucose level was more than 16.7 mmol/L were used as the diabetic group.The equivalent amount of citric acid buffer was injected in the same way in the rats of the control group.The rats were sacrificed and retinas were isolated in 4 weeks and 12 weeks after modeling.The morphology of rat retinas was examined by hematoxylin and eosin staining.The relative expression levels of phosphorylated-ERK1/2 and glial fibrillary acidic protein (GFAP)(absorption,A value) in rat retinas were detected by immunohistochemistry.Results Blood glucose levels of rats were significantly higher than those in the diabetic group compared with the control group at both 4 and 12 weeks after modeling(t=14.174,13.771,both at P＜0.05).In addition,the body weight was significantly lower and the drinking was much more in the rats of the diabetic group in comparison with the control group in 12 weeks(t=8.670,18.725,both at P＜0.05).Twelve weeks after modeling,the decrease of retinal thickness,swelling of outer plexiform layer and decline of number of retinal ganglion cells,rods and cones were seen under the optical microscope.The relative expression levels of GFAP in the retinas were 3 197.1 ±13.1 and 7 202.0±56.8 in the diabetic group at the 4 and 12 weeks,which were significantly higher than those in the control group (2 152.8 ± 16.1 and 2 337.0±8.6) (t =6.327,16.417,both at P＜0.05).In 12 weeks after modeling,the relative expression level of phosphorylated-ERK 1/2 was significantly higher in the diabetic group compared with the control group (2 850.6±2.4 versus 1 274.6± 1.3),showing a significant difference between them (t =12.771,P ＜ 0.05).Conclusions Phosphorylation of ERK1/2 signal transduction pathway is involved in the STZ-induced DR through mediating the activation of Müller cells and inducing the apoptosis of photoreceptor and ganglione cells.