Relationship Between Circulating MiRNAs And Type 2 Diabetic Non Proliferative Retinopathy

Background: Diabetic retinopathy(Diabetic retinopathy,DR)is a serious ocular disease,it is one of the major complications of diabetes,its main characteristic is retinal microvascular dysfunction,the most serious consequence is the leading cause of blindness,it has become the most leading cause of blindness in patients with diabetes mellitus.MicroRNA(miRNA)is a class of endogenous small non encoding length of single stranded RNA 19~24 RNA,a large number of studies show that miRNAs is a new type of biological markers in clinical diagnosis,there are many successful cases of miRNAs in the study of biomarkers for disease diagnosis,the relationship between circulating miRNAs and diabetic retinopathy has not been clear.Objective: To obtain the circulating miRNAs of differential expression in the development of non proliferative retinopathy of type 2 diabetes mellitus,large sample validation screening out of circulating miRNAs,through the(Receiver operating characteristic curve,ROC)curve prediction and diagnosis value of circulating miRNAs in patients with type 2 diabetes mellitus non proliferative retinopathy,provide a reliable basis for reasonable evaluation of circulating miRNAs as biomarkers for diagnosis and treatment of type 2 diabetic non proliferative retinopathy.Methods: In this study,all samples are from Shenzhen City,Nanshan District hospital for chronic diseases,the serum samples from 144 cases of healthy group,70 cases of prediabetes group,117 cases of type diabetes 2 mellitus and 75 cases type 2 diabetic non proliferative retinopathy.The samples of type 2 diabetic non proliferative retinopathy were confirmed by fundus fluorescein angiography.We performed miRNA microarray analysis from the serum of 5 health controls,5 prediabetes patients,5 type 2 diabetes mellitus patients and 5 type 2 diabetic non proliferative retinopathy patients,and then through the cluster analysis of gene chip results,we screened out the differentially expressed circulating miRNAs,which may be closely related to the development of type 2 diabetic non proliferative retinopathy,a further detection in expanded sample size was performed using quantitative real-time PCR(qRT-PCR)method by relative quantitative analysis,in order to find the circulating miRNAs related to the development of type 2 diabetic non proliferative retinopathy.Results: Based on the result of the microarray screening,finally found four miRNAs(miR-3197,miR-2116-5P,miR-3939,miR-1910-3P)were significant difference between type 2 diabetic non proliferative retinopathy group and type 2 diabetes mellitus group,however,there was no significant difference in the expression of miRNAs between prediabetes group,healthy group and type 2 diabetes mellitus group.To further verify the larger samples by using qRT-PCR technology,the results showed that the expression level of miR-3197 and miR-2116-5P were significantly higher in type 2 diabetic non proliferative retinopathy group than in type 2 diabetes mellitus group,which was statistically significant(P<0.001),and the area under the receiver operating characteristic(ROC)curve was 0.967 and 0.760 respectively.Conclusion: Circulating miR-2116-5p and circulating miR-3197 expression level in patients type 2 diabetic non proliferative retinopathy group were significantly higher than that of type 2 diabetes mellitus group,consistent with the microarray results,suggesting that circulating miR-2116-5p and circulating miR-3197 are expected as early diagnosis biomarkers of type 2 diabetic non proliferative retinopathy.