{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T02:07:28Z","timestamp":1773108448926,"version":"3.50.1"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP18H02956"],"award-info":[{"award-number":["JP18H02956"]}]},{"name":"JSPS KAKENHI","award":["JP21H03094"],"award-info":[{"award-number":["JP21H03094"]}]},{"name":"Senju Pharmaceutical Co., Ltd"},{"name":"Senju Pharmaceutical Co., Ltd"},{"name":"Senju Pharmaceutical Co., Ltd"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>We aimed to verify whether the intravitreal injection of small molecule compounds alone can create photoreceptor cells in mouse models of retinal degeneration. Primary cultured mouse M\u00fcller cells were stimulated <jats:italic>in vitro<\/jats:italic> with combinations of candidate compounds and the rhodopsin expression was measured on day 7 using polymerase chain reaction and immunostaining. We used 6-week-old N-methyl-N-nitrosourea-treated and 4-week-old rd10 mice as representative <jats:italic>in vivo<\/jats:italic> models of retinal degeneration. The optimal combination of compounds selected via <jats:italic>in vitro<\/jats:italic> screening was injected into the vitreous and the changes in rhodopsin expression were investigated on day 7 using polymerase chain reaction and immunostaining. The origin of rhodopsin-positive cells was also analyzed via lineage tracing and the recovery of retinal function was assessed using electroretinography. The <jats:italic>in vitro<\/jats:italic> mRNA expression of rhodopsin in M\u00fcller cells increased 30-fold, and 25% of the M\u00fcller cells expressed rhodopsin protein 7 days after stimulation with a combination of 4 compounds: transforming growth factor-\u03b2 inhibitor, bone morphogenetic protein inhibitor, glycogen synthase kinase 3 inhibitor, and \u03b3-secretase inhibitor. The <jats:italic>in vivo<\/jats:italic> rhodopsin mRNA expression and the number of rhodopsin-positive cells in the outer retina were significantly increased on day 7 after the intravitreal injection of these 4 compounds in both N-methyl-N-nitrosourea-treated and rd10 mice. Lineage tracing in td-Tomato mice treated with N-methyl-N-nitrosourea suggested that the rhodopsin-positive cells originated from endogenous M\u00fcller cells, accompanied with the recovery of the rhodopsin-derived scotopic function. It was suggested that rhodopsin-positive cells generated by compound stimulation contributes to the recovery of retinal function impaired by degeneration.<\/jats:p>","DOI":"10.1371\/journal.pone.0282174","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T18:33:11Z","timestamp":1677177191000},"page":"e0282174","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rhodopsin-positive cell production by intravitreal injection of small molecule compounds in mouse models of retinal 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