April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Nsaids Eye Drop As Anti-oxidant Treatment In Choroidal Neovascularization
Author Affiliations & Notes
  • Narimasa Yoshinaga
    Ophthalmology,
    Kagoshima University, Kagoshima, Japan
  • Noboru Arimura
    Ophthalmology,
    Kagoshima University, Kagoshima, Japan
  • Shozo Sonoda
    Ophthalmology,
    Kagoshima University, Kagoshima, Japan
  • Kazunori Takenouchi
    Laboratory and Vascular Medicine Cardiovascular and Respiratory Disorders Advanced Therapeutics,
    Kagoshima University, Kagoshima, Japan
  • Yukari Sadamura
    Division of Respiratory Medicine, Respirology and Stress Care Center,
    Kagoshima University, Kagoshima, Japan
  • Satoshi Noma
    Division of Respiratory Medicine, Respirology and Stress Care Center,
    Kagoshima University, Kagoshima, Japan
  • Ko-ichi Kawahara
    Laboratory and Vascular Medicine Cardiovascular and Respiratory Disorders Advanced Therapeutics,
    Kagoshima University, Kagoshima, Japan
  • Teruto Hashiguchi
    Laboratory and Vascular Medicine Cardiovascular and Respiratory Disorders Advanced Therapeutics,
    Kagoshima University, Kagoshima, Japan
  • Ikuro Maruyama
    Systems Biology in Thromboregulation,
    Kagoshima University, Kagoshima, Japan
  • Taiji Sakamoto
    Ophthalmology,
    Kagoshima University, Kagoshima, Japan
  • Footnotes
    Commercial Relationships  Narimasa Yoshinaga, None; Noboru Arimura, None; Shozo Sonoda, None; Kazunori Takenouchi, None; Yukari Sadamura, None; Satoshi Noma, None; Ko-ichi Kawahara, None; Teruto Hashiguchi, None; Ikuro Maruyama, None; Taiji Sakamoto, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2332. doi:https://doi.org/
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      Narimasa Yoshinaga, Noboru Arimura, Shozo Sonoda, Kazunori Takenouchi, Yukari Sadamura, Satoshi Noma, Ko-ichi Kawahara, Teruto Hashiguchi, Ikuro Maruyama, Taiji Sakamoto; Nsaids Eye Drop As Anti-oxidant Treatment In Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2332. doi: https://doi.org/.

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

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Abstract

Purpose: : Nonsteroidal anti-inflammatory drugs (NSAIDs) are common therapeutic agents for ocular inflammatory diseases with less adverse effect. We intended to analyze the effect of NSAIDs on induction of anti-oxidant proteins and its association with neovascularization, in both human retinal pigment epithelial (RPE) cells and a rat model of choroidal neovascularization (CNV).

Methods: : We treated human RPE cell line, ARPE-19, with NSAIDs, or vehicle control. After treatment, inductions of transcription factor NF-E2 related factor 2 (Nrf2) in nuclear protein and its downstream anti-oxidant protein heme oxygenase-1 (HO-1) in cytosolic protein were assessed using western blots and immunohistochemistry. Expressions of Nrf2 and HO-1, infiltrations of ED1 positive macrophages at CNV lesions, and the size of CNV were analyzed in a laser-induced CNV model of rat, treated with or without NSAIDs eye drop. To focus the properties of HO-1, some rats were received additional intraperitoneal injections of stannic mesoporphyrin (SnMP), an inhibitor of HO-1, and subjected to the same examinations. Levels of vascular endothelial growth factor (VEGF) in ocular fluid of these rats were also measured using ELISA.

Results: : In vitro assays showed that NSAIDs induced translocation of Nrf2 into the nucleus and robust expression of HO-1 in ARPE-19. The treatment with NSAIDs eye drop led similar changes of Nrf2 and HO-1, decreased infiltration of ED1 positive macrophages at CNV lesion, and resulted in reduction of the CNV size. Inhibition of HO-1 with SnMP reversed these effects of NSAIDs eye drop and increased level of VEGF in the ocular fluid.

Conclusions: : Treatment with NSAIDs activates Nrf2 and induces anti-oxidant protein HO-1. NSAIDs potentially repress neovascularization with the activation of Nrf2 and HO-1, whereas the inhibition of HO-1 reverses this effect. The results suggest that the NSAIDs-induced anti-neovascular effects are associated with antioxidant proteins including HO-1. NSAIDs have promising properties in ocular neovascular diseases, with its potential anti-oxidant effect.

Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • protective mechanisms 
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