학술논문
SIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process.
Document Type
Article
Author
Kikuchi, Yuki; Sugano, Eriko; Yuki, Shiori; Tabata, Kitako; Endo, Yuka; Takita, Yuya; Onoguchi, Reina; Ozaki, Taku; Fukuda, Tomokazu; Takai, Yoshihiro; Kurose, Takahiro; Tanaka, Koichi; Honma, Yoichi; Perez, Eduardo; Stock, Maxwell; Fernández, José R.; Tamura, Masanori; Voronkov, Michael; Stock, Jeffry B.; Tomita, Hiroshi
Source
Subject
*MACULAR degeneration
*INFLAMMATION
*PHOTORECEPTORS
*WESTERN immunoblotting
*OPTICAL coherence tomography
*ZEAXANTHIN
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Language
ISSN
1661-6596
Abstract
Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses. [ABSTRACT FROM AUTHOR]