September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
MicroRNA-21 Implicated in Down-Regulation of PPAR-α in Diabetic Retinopath
Author Affiliations & Notes
  • Yusuke Takahashi
    Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Harold Hamm Diabetes Center, Oklahoma City, Oklahoma, United States
  • Qian Chen
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Harold Hamm Diabetes Center, Oklahoma City, Oklahoma, United States
  • Fangfang Qiu
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Elizabeth Moran
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Harold Hamm Diabetes Center, Oklahoma City, Oklahoma, United States
  • Matlock H Greg
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Harold Hamm Diabetes Center, Oklahoma City, Oklahoma, United States
  • Kelu Zhou
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Raju V S Rajala
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Jian-Xing (Jay) Ma
    Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Harold Hamm Diabetes Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Yusuke Takahashi, None; Qian Chen, None; Fangfang Qiu, None; Elizabeth Moran, None; Matlock Greg, None; Kelu Zhou, None; Raju Rajala, None; Jian-Xing (Jay) Ma, None
  • Footnotes
    Support  NIH grants (EY018659, EY012231, EY019309, P20GM104934), a JDRF grant (2-SRA-2014-147-Q-R), American Heart Association (14PRE20460229), an IRRF grant and OCAST grants (HR12-103 and HR13-076)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3197. doi:
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    • Get Citation

      Yusuke Takahashi, Qian Chen, Fangfang Qiu, Elizabeth Moran, Matlock H Greg, Kelu Zhou, Raju V S Rajala, Jian-Xing (Jay) Ma; MicroRNA-21 Implicated in Down-Regulation of PPAR-α in Diabetic Retinopath. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3197.

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

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Abstract

Purpose : Peroxisome proliferator-activated receptor-alpha (PPAR-α) is an important transcription factor regulating expression of numerous genes implicated in lipid metabolism, glucose metabolism and insulin resistance. Two longitudinal clinical studies reported that fenofibrate, a specific PPARα agonist, showed beneficial effects on diabetic retinopathy (DR) in type 2 diabetes patients. Our recent studies showed that PPAR-α possesses anti-inflammatory and anti-apoptotic functions, and down-regulation of PPAR-α in diabetic retina is associated with pathogenic features of DR, although its mechanism was not well-understood. MiRNAs are small non-coding RNA molecules, widely present in the body and regulate a variety of developmental, physiological and pathological processes. It was reported that dysregulation of some miRNAs expression was implicated in the development and progression of diabetes. The purpose of this study was to elucidate the role of miRNAs in the down-regulation of PPAR-α in DR.

Methods : MiRNA expression changes in the retina of 6 month-old db/db mice were examined by microarray and, further validated the changes by quantitative reverse transcription-PCR (qRT-PCR). The expression levels of PPAR-α and selected miRNAs as well as diabetic markers in both in vitro and in vivo models were examined by qRT-PCR, Western blot and histochemical analyses.

Results : The miRNA microarray and qRT-PCR results showed that expression of miR-21, known as a PPAR-α targeting miRNA, was significantly up-regulated in the retina of db/db mice. Expression levels of PPAR-α were significantly down-regulated in db/db mouse retinas, whereas significantly up-regulated in the retina of miR-21 knockout mice. Similarly, human retinal capillary endothelial cells (HRCEC) treated with diabetic stressors significantly up-regulated miR-21 and down-regulated PPAR-α. Furthermore, transfection of miR-21 mimic in HRCEC resulted in significant down-regulation of PPAR-α, whereas miR-21 inhibitor significantly up-regulated the expression of PPAR-α.

Conclusions : The present study showed that the up-regulation of miR-21 in the retina of diabetic mice is responsible, at least in part, to the down-regulation of PPAR-α, which plays an important role in DR. Our studies also suggest that knock-down of miR-21 in the retina offers a therapeutic benefit to reduce inflammatory responses, oxidative stress and neuronal apoptosis in DR.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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