Serum microRNA-126 expression as a biomarker of diabetic retinopathy

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Ni Made Ayu Surasmiati
Ni Made Ari Suryathi
Ari Andayani


Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus (DM). Diabetic retinopathy causes permanent blindness in the productive age group and has a multifactorial pathogenesis. MicroRNA-126 (miRNA-126) regulates the expression of the vascular endothelial growth factor (VEGF) gene at the post-transcriptional level, VEGF being an important angiogenic protein regulating inflammation in DR development. This study aimed to determine serum miRNA-126 expression as a biomarker in DM patients with DR.

This was a cross-sectional study involving 4 healthy persons and 21 type 2 DM patients. Subjects consisted of 4 groups: i) healthy controls, ii) DM patients without diabetic retinopathy (NDR), iii) DM patients with non-proliferative DR (NPDR) and iv) DM patients with proliferative DR (PDR). Venous blood was collected from subjects for miRNA-126 examination by real-time polymerase chain reaction (PCR). MiRNA-126 in each group was analyzed using the One Way Anova test and p<0.05 was considered to be statistically significant.

Mean miRNA-126 expression was significantly decreased in PDR (1.86±1.03) and NPDR (1.01±0.43 ) groups when compared to healthy control (2.44±1.29) and NDR groups (2.15± 0.48) (p=0.027). MiRNA-126 values of less than 1.81 can differentiate NDR from the control group (sensitivity 83%, specificity 75%) and miRNA-126 of less than 1.56 can be used to predict NPDR when compared to the control group (sensitivity 86%, specificity 75%).

Serum miRNA-126 is a potential biomarker for screening of NPDR and NDR in type 2 DM patients, and could be considered a non-invasive diagnostic parameter.

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How to Cite
Surasmiati, N. M. A., Suryathi, N. M. A., & Andayani, A. (2023). Serum microRNA-126 expression as a biomarker of diabetic retinopathy. Universa Medicina, 42(2), 121–127.
Original Articles


Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis 2015;2:1–25. doi: 10.1186/s40662-015-0026-2

Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF diabetes atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017;128:40–50. doi: 10.1016/j.diabres.2017.03.024.

Wiley H, Chew E, Ferris FL. Nonproliferative diabetic retinopathy and diabetic macular edema. In: Schachat AP, Wilkinson CP, Hinton DR, Sadda SR,Wiedemann P, editors. Ryan’s Retina. 6th ed. London: Elsevier; 2018.p.3210–304.

Sun J, Silva P, Cavallerano J, et al. Proliferative diabetic retinopathy. In: Schachat AP, Wilkinson CP, Hinton DR, Sadda SR, Wiedemann P, editors. Ryan’s Retina. 6th ed. London: Elsevier; 2018.p.3305–48.

Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology 2016;123:1251–359. doi: 10.1016/j.ophtha.2016.02.022.

Zhao Y, Singh RP. The role of anti-vascular endothelial growth factor (anti-VEGF) in the management of proliferative diabetic retinopathy. Drugs Context 2018;7:1–10. doi: 10.7573/dic.212532.

Wang Y, Yan H. MicroRNA-126 contributes to Niaspan treatment induced vascular restoration after diabetic retinopathy. Sci Rep 2016;6:26909. doi: 10.1038/srep26909.

Zampetaki A, Willeit P, Burr S, et al. Angiogenic microRNAs linked to incidence and progression of diabetic retinopathy in type 1 diabetes. Diabetes 2016;65:216–27. doi: 10.2337/db15-0389.

Liu Y, Gao G, Yang C, et al. The role of circulating microRNA-126 (miR-126): a novel biomarker for screening prediabetes and newly diagnosed type 2 diabetes mellitus. Int J Mol Sci 2014;15:10567–77. doi: 10.3390/ijms150610567.

Barutta F, Bruno G, Matullo G, et al. MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study. Acta Diabetol 2017;54:133–9. doi: 10.1007/s00592-016-0915-4.

Qin LL, An MX, Liu YL, Xu HC, Lu ZQ. MicroRNA-126: a promising novel biomarker in peripheral blood for dabetic retinopathy. Int J Ophthalmol 2017;10:530–4. doi: 10.18240/ijo.2017.04.05.

Rezk NA, Sabbah NA, Saad MSS. Role of microRNA 126 in screening, diagnosis, and prognosis of diabetic patients in Egypt. IUBMB Life 2016;68:452–8. doi: 10.1002/iub.1502.

Kamel N, Ayoub N, Ibrahim R, Ghalwash A, Khalaf N. Clinical significance of microRNA 126 in diabetic retinopathy in type 2 diabetes mellitus. J Recent Adv Med 2020;1:128–35. doi: 10.21608/JRAM.2020.112534.

Pramanik S, Saha C, Chowdhury S, Bose C, Bhattacharyya NP, Mondal LK. Decreased levels of miR-126 and miR-132 in plasma and vitreous humor of non-proliferative diabetic retinopathy among subjects with type-2 diabetes mellitus. Diabetes Metab Syndr Obes 2022;15:345–58. doi: 10.2147/DMSO.S346097.

Shaker OG, Abdelaleem OO, Mahmoud RH, et al. Diagnostic and prognostic role of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in diabetic retinopathy. IUBMB Life 2019;71:310–20. doi: 10.1002/iub.1970.

Qing S, Yuan S, Yun C, et al. Serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy. Cell Physiol Biochem 2014;34:1733–40. doi: 10.1159/000366374.

Rawlings-Goss RA, Campbell MC, Tishkoff SA. Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers. BMC Med Genomics 2014;7:53.

Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc 2008;3:1101–8. doi: 10.1038/nprot.2008.73.

Prado MSG, de Goes TC, de Jesus ML, Mendonça LSO, Nascimento JS, Kaneto CM. Identification of miR-328-3p as an endogenous reference gene for the normalization of miRNA expression data from patients with diabetic retinopathy. Sci Rep 2019;9:19677. doi: 10.1038/s41598-019-56172-w.

Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan Republik Indonesia. Laporan Riset Kesehatan Dasar 2018. Lembaga Penerbit Balitbangkes. Jakarta; 2018.

Ye P, Liu J, He F, Xu W, Yao K. Hypoxia-induced deregulation of miR-126 and its regulative effect on VEGF and MMP-9 expression. Int J Med Sci 2014;11:17–23. doi: 10.7150/ijms.7329.

Shi L, Kim AJ, Chang RCA, et al. Deletion of miR-150 exacerbates retinal vascular overgrowth in high-fat-diet induced diabetic mice. PLoS One 2016;11:e0157543. doi: 10.1371/journal.pone. 0157543.

Li EH, Huang QZ, Li GC, Xiang ZY, Zhang X. Effects of miRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene. Biosci Rep 2017;37: BSR20160572. doi: 10.1042/BSR20160572.

Chen N, Wang J, Hu Y, et al. MicroRNA-410 reduces the expression of vascular endothelial growth factor and inhibits oxygen-induced retinal neovascularization. PLoS One 2014;9:e95665. doi: 10.1371/journal.pone.0095665.s002.

Fang S, Ma X, Guo S, Lu J. MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1. Oncol Lett 2017;14:4311–8. doi: 10.3892/ol.2017.669526.

Mishra S, Rizvi A, Pradhan A, Perrone MA, Ali W. Circulating microRNA-126 &122 in patients with coronary artery disease: correlation with small dense LDL. Prostaglandins Other Lipid Mediat 2021;153:106536. doi: 10.1016/j.prostaglandins.2021.106536.

Fu X, Niu T, Li X. MicroRNA-126-3p attenuates intracerebral hemorrhage-induced blood-brain barrier disruption by regulating VCAM-1 expression. Front Neurosci 2019.13:866. doi: 10.3389/fnins.2019.00866.