May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Diabetes Suppresses Retinal Expression of PPAR ; Correlation With Oxidative Stress and Vascular Inflammation
Author Affiliations & Notes
  • M. A. Al-Shabrawey
    Oral Biology/Sch of Dentistry, Medical College of Georgia, Augusta, Georgia
  • T. L. Sanders
    Oral Biology/Sch of Dentistry, Medical College of Georgia, Augusta, Georgia
  • A. M. Tawfik
    Oral Biology/Sch of Dentistry, Medical College of Georgia, Augusta, Georgia
  • Footnotes
    Commercial Relationships  M.A. Al-Shabrawey, None; T.L. Sanders, None; A.M. Tawfik, None.
  • Footnotes
    Support  AHA00104
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1334. doi:https://doi.org/
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      M. A. Al-Shabrawey, T. L. Sanders, A. M. Tawfik; Diabetes Suppresses Retinal Expression of PPAR ; Correlation With Oxidative Stress and Vascular Inflammation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1334. doi: https://doi.org/.

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

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Abstract

Purpose: : Hyperglycemia is a major risk factor that has been linked to the development of diabetic retinopathy. Increased production of reactive oxygen species (ROS) and inflammatory markers have been shown to be associated with high glucose treatment of endothelial cells. We have reported before that NADPH oxidase is a major source of increased ROS in diabetes and oxygen-induced retinopathy. Peroxisome proliferator-activated receptor gamma (PPAR γ) is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in glucose metabolism, angiogenesis, and inflammation. Recently PPAR γ signaling pathway has been demonstrated to inhibit diabetes induced retinal leukostasis and leakage. The goal of this study was to investigate the effect of hyperglycemia on retinal expression of PPAR γ and whether this is related to the oxidative stress and vascular inflammation associated with diabetic retinopathy.

Methods: : Diabetes was induced with streptozotocin in wild type mice or mice lacking the catalytic subunit of NADPH oxidase gp91phox. One group of wild type mice was treated with NADPH oxidase inhibitor apocynin (10mg/kg in drinking water) for 5 weeks. The retinal levels of PPAR γ, ICAM-1 and activated NFΚB were evaluated with Western blotting and immunofluroscence. Expression of PPAR γ was also investigated in human umbilical vein endothelial cells (HUVECs) treated with normal glucose (NG, 5 mM) or high glucose (HG, 30 mM) in the presence or absence of superoxide dismutase (SOD), mitochondrial oxidases inhibitor; thenoyltrifluoroacetone (TTFA) or NADPH oxidase inhibitors; apocynin or diphenyliodonium (DPI). To further evaluate the interaction between NADPH oxidase and PPAR γ in mediating retinal vascular inflammation we also tested ICAM-1 and PPAR γ expression in wild type and gp91phox knockout mice injected with lipopolysccharide (LPS, 0.1 mg/kg).

Results: : Diabetes suppressed retinal expression of PPAR γ and increased the levels of ICAM-1 and activated NFΚB as shown by the increases in p-NFΚB and p-IΚB (all P<0.05). These effects were prevented by apocynin or deletion of gp91phox (P< 0.05). Furthermore, HG treatment of HUVECs suppressed PPAR γ expression and this was prevented by TTFA, apocynin, DPI and by SOD (P<0.05). Deletion of gp91phox inhibited LPS-induced ICAM-1 expression and restored PPAR γ to the normal level (P< 0.05).Conclusion There is an interaction between oxidative stress and PPAR γ in mediating vascular inflammation associated with diabetic retinopathy. Targeting this signaling pathway could be a therapeutic strategy to prevent diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation • oxidation/oxidative or free radical damage 
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