NSAIDs Induce Antioxidant Proteins in Retinal Pigment Epithelial Cells

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 antioxidant proteins in human retinal pigment epithelial (RPE) cells and in a rat model of choroidal neovascularization (CNV).

Methods: : We treated human RPE cell line, ARPE-19, with indomethacine (0-500 uM), bromfenac (0-200 uM), or vehicle control (dimethylsulfoxide). After treatment, inductions of transcription factor NF-E2 related factor 2 (Nrf2) in nuclear protein and its downstream protein heme oxygenase-1 (HO-1) in cytosolic protein were assessed using western blots. The expressions of Nrf2 and HO-1 also were examined by immunohistochemistry. In vivo expressions of Nrf2 and HO-1 were analyzed in a laser-induced CNV model of rat treated with or without bromfenac ophthalmic solution.

Results: : Western blots showed both indomethacine and bromfenac induced the translocation of Nrf2 into the nucleus and that the robust expression of HO-1 in ARPE-19 with a dose- and time- dependent manner. Immunohistochemistry also showed dose- dependent translocation of Nrf2 into the nucleus accompanied with expression of Ho-1. Additionally, analysis in vivo showed that treatment with bromfenac ophthalmic solution potentially led translocation of Nrf2 into the nucleus especially in the part of laser-induced CNV.

Conclusions: : Treatment with NSAIDs led to translocation of Nrf2 into the nucleus and induction of antioxidant protein HO-1. The results suggest that NSAIDs has properties as a potential antioxidant agent in ocular retinal diseases.

Keywords: retina • retinal pigment epithelium • oxidation/oxidative or free radical damage