{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:08Z","timestamp":1772118728899,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Retinal degenerative diseases cause irreversible vision loss due to photoreceptor degeneration. Retinal organoid transplantation offers a promising strategy for restoring vision, but assessing functional recovery remains challenging. Standard visual function tests provide binary or coarse measures that do not fully capture how visual input influences natural behavior. Here, we applied a Hidden Markov Model (HMM)\u2010based behavioral analysis to the visual cliff test to track locomotor state transitions in wild\u2010type (WT) and rd1\u20102\u2009J (RD) mice, evaluating depth perception and its recovery following photoreceptor transplantation. WT mice exhibited a strong cliff avoidance response, while RD mice showed no response, confirming the model's sensitivity to depth perception. Over repeated trials, WT mice rapidly habituated, shifting from three behavioral states (Resting, Exploring, and Navigating) to just two (Resting and Navigating). Transplanted RD mice began responding to the cliff at 2\u2009weeks posttransplantation, coinciding with early synapse formation between grafted photoreceptors and host bipolar cells. The avoidance response became robust by 16\u2009weeks but disappeared by 18\u2009weeks, accompanied by state collapse, a hallmark of habituation never observed in untreated RD mice. These findings demonstrate that behavioral state\u2010based analysis provides a sensitive and dynamic measure of functional vision recovery, capturing not only the emergence of depth perception but also its integration into adaptive behavior. This approach may help refine clinical evaluations of vision restoration therapies, bridging the gap between sensory recovery and real\u2010world functional outcomes.<\/jats:p>","DOI":"10.1002\/jnr.70068","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T10:00:20Z","timestamp":1753264820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hidden Markov Model\u2010Based Behavioral Classification Reveals Visual Function Recovery After Retinal Organoid Transplantation in Mice"],"prefix":"10.1002","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0343-3132","authenticated-orcid":false,"given":"Hironobu","family":"Shuto","sequence":"first","affiliation":[{"name":"Vision Care Inc.  Kobe Hyogo Japan"},{"name":"Graduate School of Pharmacy Ritsumeikan University  Kusatsu Siga Japan"},{"name":"Laboratory for Animal Resources and Genetic Engineering RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiko","family":"Mandai","sequence":"additional","affiliation":[{"name":"Laboratory for Animal Resources and Genetic Engineering RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"},{"name":"Research Center Kobe City Eye Hospital  Kobe Hyogo Japan"},{"name":"Research Organization of Science and Technology Ritsumeikan University  Kusatsu Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Yamada","sequence":"additional","affiliation":[{"name":"Vision Care Inc.  Kobe Hyogo Japan"},{"name":"Laboratory for Animal Resources and Genetic Engineering RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junki","family":"Sho","sequence":"additional","affiliation":[{"name":"Vision Care Inc.  Kobe Hyogo Japan"},{"name":"Laboratory for Animal Resources and Genetic Engineering RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chihiro","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Vision Care Inc.  Kobe Hyogo Japan"},{"name":"Laboratory for Animal Resources and Genetic Engineering RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chieko","family":"Koike","sequence":"additional","affiliation":[{"name":"Center for Systems Vision Science, Organization of Science and Technology Ritsumeikan University  Kusatsu Shiga Japan"},{"name":"Ritsumeikan Global Innovation Research Organization (R\u2010GIRO), Ritsumeikan University  Kusatsu Siga Japan"},{"name":"College of Pharmaceutical Science Ritsumeikan University  Kusatsu Siga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayo","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Vision Care Inc.  Kobe Hyogo Japan"},{"name":"Ritsumeikan Advanced Research Academy Ritsumeikan University  Kusatsu Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2092-7519","authenticated-orcid":false,"given":"Take","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Vision Care Inc.  Kobe Hyogo Japan"},{"name":"Laboratory for Animal Resources and Genetic Engineering RIKEN Center for Biosystems Dynamics Research  Kobe Hyogo Japan"},{"name":"Research Center Kobe City Eye Hospital  Kobe Hyogo Japan"},{"name":"Research Organization of Science and Technology Ritsumeikan University  Kusatsu Shiga Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/2041\u2010210X.13241"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014\u20102999(03)01274\u20103"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007\u20100804"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40462\u2010020\u20100195\u2010z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.applanim.2016.08.005"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.08.007"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00055.2017"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.166"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2016.12.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100209\u2010y"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102866"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00359\u2010006\u20100093\u2010x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3791\/52434"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","unstructured":"Shuto H. T.Maeda C.Koike M.Takahashi M.Mandai andT.Matsuyama. n.d.\u201cHidden Markov Models Reveal Complex Depth Processing in Mouse Visual Behavior.\u201dhttps:\/\/doi.org\/10.1101\/2025.07.09.663818. Under Submission.","DOI":"10.1101\/2025.07.09.663818"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010020\u20100776\u2010y"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.70068","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T13:16:11Z","timestamp":1753362971000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.70068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":16,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/jnr.70068"],"URL":"https:\/\/doi.org\/10.1002\/jnr.70068","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/JNR.70068\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v3\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/JNR.70068\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70068"}}