June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Circulating MicroRNA (miRNA) Expression Signatures in Type 1 diabetic (T1D) Individuals Protected from Development of Diabetic Retinopathy (DR)
Author Affiliations & Notes
  • Maria B Grant
    Indiana University School of Medicine, Indianapolis, IN
    Ophthalmology, IUPUI, Indianapolis, IN
  • David Kent
    Ophthalmology, Aut Even Hospital Kilkenny, Liverpool, United Kingdom
  • Robert N Mames
    Retina Center, Gainesville, FL
  • Ashay D Bhatwadekar
    Ophthalmology, IUPUI, Indianapolis, IN
  • L Yan
    Cell Bilogy, SUNY Downstate Medical Center, Brooklyn, NY
  • H Chintala
    Cell Bilogy, SUNY Downstate Medical Center, Brooklyn, NY
  • Brahim Chaqour
    Cell Bilogy, SUNY Downstate Medical Center, Brooklyn, NY
  • Footnotes
    Commercial Relationships Maria Grant, None; David Kent, None; Robert Mames, None; Ashay Bhatwadekar, None; L Yan, None; H Chintala, None; Brahim Chaqour, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 48. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×