@article{4482,
  keywords = {Animals, Rats, Retina, Light, Anti-Inflammatory Agents, Lipopolysaccharides, Photoreceptor Cells, Vertebrate, Electroretinography, Retinal Degeneration},
  author = {Yuki Kikuchi and Eriko Sugano and Shiori Yuki and Kitako Tabata and Yuka Endo and Yuya Takita and Reina Onoguchi and Taku Ozaki and Tomokazu Fukuda and Yoshihiro Takai and Takahiro Kurose and Koichi Tanaka and Yoichi Honma and Eduardo P{\'e}rez and Maxwell Stock and Jos{\'e} Fern{\'a}ndez and Masanori Tamura and Michael Voronkov and Jeffry Stock and Hiroshi Tomita},
  title = {SIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process.},
  abstract = { <p>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 M{\"u}ller 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.</p> },
  year = {2022},
  journal = {Int J Mol Sci},
  volume = {23},
  month = {2022 Aug 08},
  issn = {1422-0067},
  doi = {10.3390/ijms23158802},
  language = {eng},
}