The involvement of ATF4 and S-opsin in retinal photoreceptor cell damage induced by blue LED light.
Blue light is a high-energy emitting light with a short wavelength in the visible light spectrum. Blue light induces photoreceptor apoptosis and causes age-related macular degeneration or retinitis pigmentosa. In the present study, we investigated the roles of endoplasmic reticulum (ER) stress induced by blue light-emitting diode (LED) light exposure in murine photoreceptor cells.



The murine photoreceptor cell line was incubated and exposed to blue LED light (464 nm blue LED light, 450 lx, 3 to 24 h). The expression of the factors involved in the unfolded protein response pathway was examined using quantitative real-time reverse transcription (RT)-PCR and immunoblot analysis. The aggregation of short-wavelength opsin (S-opsin) in the murine photoreceptor cells was observed with immunostaining. The effect of S-opsin knockdown on ATF4 expression in the murine photoreceptor cell line was also investigated.



Exposure to blue LED light increased thebip,atf4, andgrp94mRNA levels, induced the expression of ATF4 protein, and increased the levels of ubiquitinated proteins. Exposure to blue LED light in combination with ER stress inducers (tunicamycin and dithiothreitol) induced the aggregation of S-opsin. S-opsin mRNA knockdown prevented the induction of ATF4 expression in response to exposure to blue LED light.



These findings indicate that the aggregation of S-opsin induced by exposure to blue LED light causes ER stress, and ATF4 activation in particular.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan; Wakasa Seikatsu Co. Ltd, 22 Naginataboko-cho, Shijo-Karasuma, Shimogyo-ku, Kyoto, Japan.
Emi
E
Ooe
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan.
Kazuhiro
K
Tsuruma
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan.
Yoshiki
Y
Kuse
Wakasa Seikatsu Co. Ltd, 22 Naginataboko-cho, Shijo-Karasuma, Shimogyo-ku, Kyoto, Japan.
Saori
S
Kobayashi
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan.
Masamitsu
M
Shimazawa
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Daigakunishi, Gifu, Japan.
Hideaki
H
Hara
D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004229:Dithiothreitol / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D008027:Light; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D025821:Polyubiquitin / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D054875:Ubiquitination / Q000187:drug effects / Q000528:radiation effects; D056811:Unfolded Protein Response / Q000187:drug effects / Q000528:radiation effects
C081452:Atf4 protein, mouse; D066329:Protein Aggregates; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017299:Rod Opsins; C095853:short-wavelength opsin; D014415:Tunicamycin; D025821:Polyubiquitin; D051701:Activating Transcription Factor 4; D004229:Dithiothreitol