SIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process.

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.

• Authors: Yuki Kikuchi, Eriko Sugano, Shiori Yuki, Kitako Tabata, Yuka Endo, Yuya Takita, Reina Onoguchi, Taku Ozaki, Tomokazu Fukuda, Yoshihiro Takai, Takahiro Kurose, Koichi Tanaka, Yoichi Honma, Eduardo Perez, Maxwell Stock, José R Fernández, Masanori Tamura, Michael Voronkov, Jeffry B Stock, Hiroshi Tomita
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 15 (Aug 08 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35955937 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Lipopolysaccharides

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Electroretinography
• Light
• Lipopolysaccharides (pharmacology)
• Photoreceptor Cells, Vertebrate
• Rats
• Retina
• Retinal Degeneration (drug therapy, etiology)