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

TitleSIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process.
Publication TypeJournal Article
Year of Publication2022
AuthorsKikuchi, Y, Sugano, E, Yuki, S, Tabata, K, Endo, Y, Takita, Y, Onoguchi, R, Ozaki, T, Fukuda, T, Takai, Y, Kurose, T, Tanaka, K, Honma, Y, Pérez, E, Stock, M, Fernández, JR, Tamura, M, Voronkov, M, Stock, JB, Tomita, H
JournalInt J Mol Sci
Volume23
Issue15
Date Published2022 Aug 08
ISSN1422-0067
KeywordsAnimals, Anti-Inflammatory Agents, Electroretinography, Light, Lipopolysaccharides, Photoreceptor Cells, Vertebrate, Rats, Retina, Retinal Degeneration
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 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.</p>

DOI10.3390/ijms23158802
Alternate JournalInt J Mol Sci
PubMed ID35955937
PubMed Central IDPMC9369167
Grant List21K18278, 19H03807, 19K09945, and 21K09713 / / Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan /