Serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy.

Diabetic retinopathy (DR) is a retinopathy resulting from diabetes mellitus (DM) which was classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs) that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA). The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR) arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC) curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

Qing S ，Yuan S ，Yun C ，Hui H ，Mao P ，Wen F ，Ding Y ，Liu Q ... -  《-》

Diagnostic and prognostic role of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in diabetic retinopathy.

Noncoding RNAs are emerging biomarkers for many diseases including diabetic retinopathy (DR). This study aimed to measure the expression levels of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in DR patients. A total of 80 patients diagnosed as type 2 diabetes (T2D) and 81 healthy subjects were recruited in this study. T2D patients were divided into three groups: nondiabetic retinopathy (NDR) group (30 patients), nonproliferative diabetic retinopathy (NPDR) group (30 patients), and proliferative diabetic retinopathy (PDR) group (20 patients). Quantitative real-time polymerase chain reaction (PCR) was used to assess the expression of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1. We found a significant decrease in serum miR-20b and a significant increase in serum HOTAIR and MALAT1 in NDR patients compared to healthy subjects. Also, we revealed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in each of NPDR and PDR groups when compared with healthy subjects. Furthermore, we reported a significant decrease in miR-20b and miR-17-3p and a significant increase in HOTAIR and MALAT1in DR as well as in PDR patients when compared with NDR patients. However, on comparing NPDR with NDR patients, no significant difference was observed regarding the expression levels of miR-20b and miR-17-3p, in contrast, significant elevation of serum HOTAIR and MALAT1 was found in NPDR. Moreover, we observed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in PDR group relative to NPDR group. Receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of the examined serum noncoding RNAs as novel biochemical indicators detecting severity of DR. Our analyses suggested that the examined serum noncoding RNAs may discriminate DR (PDR and NPDR) from NDR. Furthermore, these noncoding RNAs (less importantly miR-17) can be used as promising novel biomarkers for prediction DR severity, distinguishing PDR from NPDR patients. We can conclude that serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 may be used as noninvasive biomarkers for screening of DR and early diagnosis of PDR. © 2018 IUBMB Life, 71(3):310-320, 2019.

Shaker OG ，Abdelaleem OO ，Mahmoud RH ，Abdelghaffar NK ，Ahmed TI ，Said OM ，Zaki OM ... -  《-》

RNA sequencing identified specific circulating miRNA biomarkers for early detection of diabetes retinopathy.

Liang Z ，Gao KP ，Wang YX ，Liu ZC ，Tian L ，Yang XZ ，Ding JY ，Wu WT ，Yang WH ，Li YL ，Zhang ZB ，Zhai RH ... -  《-》

Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood.

This study aimed to determine whether circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for proliferative diabetic retinopathy (PDR). This retrospective cross-sectional study comprised 34 healthy participants, 34 PDR patients and 34 non-proliferative DR (NPDR) patients. High-throughput whole transcriptome sequencing was performed to explore the expression profile of circRNAs in the whole blood, and the candidate circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis evaluated the ability of these candidate circRNAs in discriminating PDR patients from NPDR patients and healthy subjects. Finally, the networks of circRNA-miRNA-mRNA based on the candidate circRNAs were constructed. Using sequencing and qRT-PCR, hsa_circ_0001953 was found to be elevated in PDR patients in contrast with the other two groups. Statistical analysis showed that the expression levels of hsa_circ_0001953 in PDR patients were positively related to the duration of diabetes and HbAc1. Receiver operating characteristic (ROC) curve analysis revealed that hsa_circ_0001953 was associated with a high diagnostic accuracy in discriminating PDR patients from NPDR patients and healthy controls, resulting in an area under the curve (AUC) of 0.87 and 0.92, respectively. The circRNA-miRNA-target gene networks for hsa_circ_0001953 showed that hsa_circ_0001953 could interact with dozens of miRNAs and some targeted mRNAs have been potentially involved in the pathogenesis of diabetes. The present findings indicate that hsa_circ_0001953 in the whole blood may serve as a novel diagnostic biomarker and potential therapeutic target for PDR.

Wu Z ，Liu B ，Ma Y ，Chen H ，Wu J ，Wang J ... -  《-》

Serum miR-122 levels correlate with diabetic retinopathy.

Pastukh N ，Meerson A ，Kalish D ，Jabaly H ，Blum A ... -  《-》