July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
miRNA15 Regulates Insulin Signal Transduction in the Retinal Vasculature
Author Affiliations & Notes
  • Youde Jiang
    Wayne State University, Madison Heights, Michigan, United States
  • Li Liu
    Wayne State University, Madison Heights, Michigan, United States
  • Jena J Steinle
    Wayne State University, Madison Heights, Michigan, United States
  • Footnotes
    Commercial Relationships   Youde Jiang, None; Li Liu, None; Jena Steinle, None
  • Footnotes
    Support  NIH EYR01022045, P30EY04068, RPB Department Award
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3540. doi:
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    • Get Citation

      Youde Jiang, Li Liu, Jena J Steinle; miRNA15 Regulates Insulin Signal Transduction in the Retinal Vasculature. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3540.

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

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Abstract

Purpose : To investigate whether miR15a could regulate insulin signaling in the retinal vasculature and in retinal endothelial cells (REC)

Methods : Using endothelial cell specific miR15a floxed and Cre-Lox mice, as well as miR15a overexpressing mice, we investigated proteins levels of phosphorylated insulin receptor, phosphorylated Akt, phosphorylated IRS-1Ser307, and cleaved caspase 3 in whole retinal lysates. We also grew primary human REC in normal and high glucose and measured the same insulin signaling proteins. Some REC were treated with reservatrol, which has been shown to increase miR15a expression in cancer cells. A binding assay was done to investigate whether the insulin receptor is a direct target of miR15a.

Results : We found that miR15a directly binds the insulin receptor. In mouse retina, loss of miR15a led to a decrease in insulin and Akt phosphorylation, while increased IRS-1Ser307 phosphorylation and the cleavage of caspase 3. REC grown in high glucose had reduced insulin receptor signaling, which was restored by treatment with resveratrol.

Conclusions : miR15a directly binds to the insulin receptor. Unlike most miRNA that repress gene expression, data in the mice show that miR15a increased insulin levels and signal transduction. Work in REC treated with reservatrol to increase miR15a expression also had increased insulin signaling, with decreased phosphorylation of IRS-1 on serine 307. Future work will focus on the regulatory mechanisms of miR15a on insulin signaling.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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