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Maria B Grant, David Kent, Robert N Mames, Ashay D Bhatwadekar, L Yan, H Chintala, Brahim Chaqour; Circulating MicroRNA (miRNA) Expression Signatures in Type 1 diabetic (T1D) Individuals Protected from Development of Diabetic Retinopathy (DR). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):48.
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Despite less than optimal glucose control and long standing disease, some diabetics remain free of microvascular complications. To better characterize these individuals “protected” from DR, we examined circulating miRNAs. We compared the expression profile of circulating miRNAs in three groups (n=10/group): 1) individuals with > 40 years of T1D without DR; 2) individuals with >40 years of T1D with proliferative DR matched in age, sex and glycemic control to group 1; and 3) age-sex matched non-diabetic controls.
Serum samples were collected from the three cohorts. miRNAs were prepared and analyzed with the Qiagen Serum and Plasma microRNA Array. Data analysis was performed with the Qiagen miScript Data Analysis Tool. MirPATH software was used to create relational patterns between miRNAs and signaling pathways.
In DR individuals, 52 circulating miRNAs were upregulated and 4 miRNAs were downregulated when compared to controls. Individuals protected from DR displayed a distinct serum miRNA profile with 19 miRNAs upregulated and 45 miRNAs downregulated. Interestingly, when comparing the circulating miRNA profile of DR individuals with protected individuals, 19 miRNAs displayed opposite expression patterns (let-7a, miR-10b, miR-126, miR-150, miR-155, miR-18a, miR-200b, miR-20a, miR-222, miR-224, miR-27a, miR-93, let-7c, miR-10a, miR-15a, miR-30e, miR-372, miR-191, and miR-26a). These miRNAs were upregulated in the serum of DR individuals but were downregulated in the serum of protected individuals, indicating a relationship between miRNA expression signatures and susceptibility to DR. Using miRPATH, a computer based software that performs hierarchical clustering of miRNAs and pathways based on their interaction levels, we found that eight (let-7a, miR-155, miR-20a, miR-27a, let-7c, miR-30e, miR-26a, and mir-15a) of the 19 miRNAs largely affect the same angiogenic pathways of phosphoinositol-3 kinase (PI3K)/Akt, Wnt, and mitogen-activated protein kinase (MAPK).
Our results identified a distinct miRNA profile in the serum of individuals protected from development of DR despite > 40 years of TID. MiRNAs that influence PI3K/Akt, Wnt, and MAPK signaling were reduced in these protected individuals suggesting that serum miRs may represent biomarkers of DR and that these miRs may represent potential therapeutic targets for DR.
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