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