June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
THE PATHOGENIC ROLE OF DOWN-REGULATION OF PPAR-ΑLPHA EXPRESSION IN DIABETIC RETINOPATHY
Author Affiliations & Notes
  • Yang Hu
    Physiology, OUHSC, Oklahoma City, OK
  • Ying Chen
    Physiology, OUHSC, Oklahoma City, OK
    Harold Hamm Diabetes Center, OUHSC, oklahoma, OK
  • Lexi Ding
    Physiology, OUHSC, Oklahoma City, OK
  • Xuemin He
    Physiology, OUHSC, Oklahoma City, OK
  • Yusuke Takahashi
    Harold Hamm Diabetes Center, OUHSC, oklahoma, OK
  • Rui Cheng
    Physiology, OUHSC, Oklahoma City, OK
  • Yang Gao
    Physiology, OUHSC, Oklahoma City, OK
  • Wei Shen
    Physiology, OUHSC, Oklahoma City, OK
  • Qian Chen
    Physiology, OUHSC, Oklahoma City, OK
  • Jian-Xing Ma
    Physiology, OUHSC, Oklahoma City, OK
    Harold Hamm Diabetes Center, OUHSC, oklahoma, OK
  • Footnotes
    Commercial Relationships Yang Hu, None; Ying Chen, None; Lexi Ding, None; Xuemin He, None; Yusuke Takahashi, None; Rui Cheng, None; Yang Gao, None; Wei Shen, None; Qian Chen, None; Jian-Xing Ma, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1152. doi:https://doi.org/
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      Yang Hu, Ying Chen, Lexi Ding, Xuemin He, Yusuke Takahashi, Rui Cheng, Yang Gao, Wei Shen, Qian Chen, Jian-Xing Ma; THE PATHOGENIC ROLE OF DOWN-REGULATION OF PPAR-ΑLPHA EXPRESSION IN DIABETIC RETINOPATHY. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1152. doi: https://doi.org/.

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

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Abstract

Purpose: Diabetic retinopathy is a common cause of vision loss which results from progressive pathological changes including retinal inflammation, vascular leakage, neovascularization (NV) and fibrosis. Recent clinical studies have shown that PPAR-α agonist has therapeutic effect on diabetic retinopathy. The purpose of this study is to investigate the role of PPAR-α in diabetic retinopathy.

Methods: Adult Brown Norway rats, PPAR-α knock-out (KO) mice and C57/BL6 mice were injected with Streptozotocin (STZ) to induce diabetes. PPAR-α, PPAR-β and PPAR-γ expression levels in the retina were compared between STZ-induced diabetic rats, Akita mice and db/db mice and their respective non-diabetic controls using Western blot analyses and real-time RT-PCR. PPARs protein and mRNA levels were measured in hTERT RPE cells and rat Müller cells treated with high glucose medium. Vascular permeability, leukostasis and trypsin digestion were performed in PPAR-α KO mice and C57/BL6 mice 3 months after the STZ injection. Adenovirus expressing PPAR-α was injected intravitreally into diabetic rats, with adenovirus expressing GFP as control.

Results: Both of mRNA and protein levels of PPAR-α were significantly decreased in the retinas of STZ-induced diabetic rats, Akita mice and db/db mice compared with non-diabetic controls, and in the hTERT RPE cells and rat Müller cells treated with high glucose. Retinal vascular permeability, adherent leukocytes, endothelial cell/pericyte ratio were significantly higher in STZ-induced PPAR-α KO mice compared with diabetic C57/BL6 mice. Over-expression of PPAR-α significantly reduced vascular permeability and attenuated over-expression of pro-inflammatory factors in the retinas of STZ-induced diabetic rats.

Conclusions: PPAR-α defect plays an important role in diabetic retinopathy. PPAR-α is a novel therapeutic target for diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 688 retina • 557 inflammation  
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