{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:13:37Z","timestamp":1788545617845,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T00:00:00Z","timestamp":1564099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammation and angiogenesis. In this study, we investigated the possible involvement of S1P in the pathology of light-induced retinal degeneration in vivo and in vitro. The intracellular S1P and sphingosine kinase (SphK) activity in a photoreceptor cell line (661W cells) was significantly increased by exposure to light. The enhancement of SphK1 expression was dependent on illumination, and all-trans-retinal significantly promoted SphK1 expression. S1P treatment reduced protein kinase B (Akt) phosphorylation and increased the protein expression of cleaved caspase-3, and induced photoreceptor cell apoptosis. In vivo, light exposure enhanced the expression of SphK1 in the outer segments of photoreceptors. Intravitreal injection of a SphK inhibitor significantly suppressed the thinning of the outer nuclear layer and ameliorated the attenuation of the amplitudes of a-waves and b-waves of electroretinograms during light-induced retinal degeneration. These findings imply that light exposure induces the synthesis of S1P in photoreceptors by upregulating SphK1, which is facilitated by all-trans-retinal, causing retinal degeneration. Inhibition of this enhancement may be a therapeutic target of outer retinal degeneration, including age-related macular degeneration.<\/jats:p>","DOI":"10.3390\/ijms20153670","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T08:45:39Z","timestamp":1564130739000},"page":"3670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Light Stress-Induced Increase of Sphingosine 1-Phosphate in Photoreceptors and Its Relevance to Retinal Degeneration"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6182-4343","authenticated-orcid":false,"given":"Ryo","family":"Terao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, Tokyo University, Tokyo 113-8654, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Honjo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, Tokyo University, Tokyo 113-8654, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ueta","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, Tokyo University, Tokyo 113-8654, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideru","family":"Obinata","sequence":"additional","affiliation":[{"name":"Gunma University Initiative for Advanced Research (GIAR), 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kurano","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8654, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yatomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8654, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Koso","sequence":"additional","affiliation":[{"name":"Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6810-0583","authenticated-orcid":false,"given":"Makoto","family":"Aihara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, Tokyo University, Tokyo 113-8654, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neuron.2012.06.018","article-title":"Mechanisms of age-related macular degeneration","volume":"75","author":"Ambati","year":"2012","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1056\/NEJMra062326","article-title":"Age-related macular degeneration","volume":"355","year":"2006","journal-title":"N. 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