September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Anti-inflammatory and anti-apoptotic effects of a novel agonist of peroxisome proliferator-activated receptor-alpha in ischemic retinopathy
Author Affiliations & Notes
  • GUOTAO DENG
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States
  • Elizabeth Moran
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States
  • Rui Cheng
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States
  • Danyang Chen
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States
  • Jian-Xing (Jay) Ma
    Department of Physiology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   GUOTAO DENG, None; Elizabeth Moran, None; Rui Cheng, None; Danyang Chen, None; Jian-Xing (Jay) Ma, None
  • Footnotes
    Support  NIH grants (EY018659, EY012231, EY019309 P20GM104934), JDRF grant (2-SRA-2014-147-Q-R) , OCAST grant (HR13-076).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5389. doi:
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    • Get Citation

      GUOTAO DENG, Elizabeth Moran, Rui Cheng, Danyang Chen, Jian-Xing (Jay) Ma; Anti-inflammatory and anti-apoptotic effects of a novel agonist of peroxisome proliferator-activated receptor-alpha in ischemic retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5389.

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

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Abstract

Purpose : Previous studies have shown that the peroxisome proliferator-activated receptor-alpha (PPARα) agonist fenofibrate has anti-inflammatory and anti-apoptotic effects in diabetic retinopathy. The purpose of this study was to identify novel PPARα agonists and to investigate their beneficial effects on ischemic retinopathy.

Methods : The activation of PPARα by the newly identified agonist was measured by luciferase-based promoter assay. The effect of the PPARα agonist on endothelial cell migration and tube formation was evaluated using human retinal capillary endothelial cells (HRCEC). TUNEL was used to evaluate the effect on apoptosis in human retinal Müller cells (MIO-M1) and retinal precursor cells (R28) exposed to palmitate. C57BL/6 mice were exposed to 75% oxygen from postnatal day 7 (P7) to P12, followed by exposure to room air from P12 to P17 to generate oxygen-induced retinopathy (OIR). The candidate PPARα agonist (10 mg/kg/day) and the same volume of vehicle were intraperitoneally injected daily from P12 to P16. At P17, retinal inflammation was examined using leukostasis assay, and retinal levels of inflammatory factors were measured by Western blotting. Student`s T-test was used for statistical analysis.

Results : A new compound with chemical structure distinct from existing PPARα agonists was identified which activated PPARα transcriptional activity in a concentration-dependent manner (with EC50 of 49.89 µM compared to 53.01 µM of fenofibrate). HRCEC migration and tube formation were significantly inhibited by the newly identified PPARα agonist. The compound also showed a protective effect against palmitate-induced apoptosis of human retinal Müller cells and retinal precursor cells. In the OIR model, the number of adherent leukocytes was decreased in the retinal vasculature of the mice treated with the compound compared to vehicle group (n=5, P < 0.05). In addition, retinal levels of ICAM-1, MCP-1, TNF-α were downregulated by this compound.

Conclusions : The newly identified compound is a potent PPARα agonist with distinct structure from fenofibrate and has therapeutic potential for ischemia-induced retinopathy.

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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