{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T23:24:25Z","timestamp":1766705065655,"version":"3.48.0"},"reference-count":28,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY033103"],"award-info":[{"award-number":["R01EY033103"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY030872"],"award-info":[{"award-number":["R01EY030872"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["F31EY033187"],"award-info":[{"award-number":["F31EY033187"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016383","name":"Shulsky Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["G2019300"],"award-info":[{"award-number":["G2019300"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001209","name":"Knights Templar Eye Foundation","doi-asserted-by":"publisher","award":["147042"],"award-info":[{"award-number":["147042"]}],"id":[{"id":"10.13039\/100001209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007880","name":"Johns Hopkins University","doi-asserted-by":"publisher","award":["EY001765"],"award-info":[{"award-number":["EY001765"]}],"id":[{"id":"10.13039\/100007880","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Photoreceptor transplantation is being studied to restore visual function in retinal diseases causing blindness, including age\u2010related macular degeneration, hereditary eye diseases, and traumatic retinopathy. Preclinical studies often involve delivering exogenous human photoreceptor cells into animal models' retinas. A key readout in such experiments is distinguishing donor cell integration from artificial labeling secondary to material transfer of cytosolic or nuclear labels. Recognizing donor (human) versus animal photoreceptor nuclei is key, but purely immunohistology discrimination is challenging due to antigenic species overlap or intercellular antigen transfer. To address this, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. We aim to evaluate the feasibility of computer\u2010assisted nuclear detection combined with random forest classification to automate species differentiation in DAPI\u2010stained photoreceptors after xenotransplantation into mouse and pig retinas. Our models were trained on single\u2010species samples and validated with mixed\u2010species samples. We then transplanted human embryonic stem cell\u2010derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post\u2010xenotransplantation, validated by histological assessment using an antihuman nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semiautomated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.<\/jats:p>","DOI":"10.1111\/cts.70420","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T08:12:54Z","timestamp":1764749574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of Machine Learning to Discriminate Photoreceptor Cell Species in Xenotransplanted Chimeric Retinas"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-4255","authenticated-orcid":false,"given":"Kang V.","family":"Li","sequence":"first","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-4576","authenticated-orcid":false,"given":"Annabelle","family":"Pan","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4568-7585","authenticated-orcid":false,"given":"Ying V.","family":"Liu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-1097","authenticated-orcid":false,"given":"Bani","family":"Antonio\u2010Aguirre","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0613-667X","authenticated-orcid":false,"given":"Joyce","family":"Wang","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6581-6104","authenticated-orcid":false,"given":"McKaily","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Biology Krieger School of Arts and Sciences, Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-6329","authenticated-orcid":false,"given":"Christina","family":"McNerney","sequence":"additional","affiliation":[{"name":"Department of Biology Krieger School of Arts and Sciences, Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-8379","authenticated-orcid":false,"given":"Sai Bo Bo","family":"Tun","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Center  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9058-7313","authenticated-orcid":false,"given":"Yuchen","family":"Lu","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3370-633X","authenticated-orcid":false,"given":"Zhuolin","family":"Li","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3126-1329","authenticated-orcid":false,"given":"Minda","family":"McNally","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6477-9784","authenticated-orcid":false,"given":"Veluchamy A.","family":"Barathi","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Center  Singapore Singapore"},{"name":"Ophthalmology and Visual Science Academic Clinical Program Duke\u2010NUS Medical School  Singapore Singapore"},{"name":"Department of Ophthalmology, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5775-6218","authenticated-orcid":false,"suffix":"Jr.","given":"Robert J.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Biology Krieger School of Arts and Sciences, Johns Hopkins University  Baltimore Maryland USA"},{"name":"Solomon H. Snyder Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1749-0088","authenticated-orcid":false,"given":"Mandeep S.","family":"Singh","sequence":"additional","affiliation":[{"name":"Wilmer Eye Institute Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(06)69740\u20107"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/aos.14996"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2022.4401"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2022.06.009"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.813538"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2020.06.019"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.6.3.4"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2552"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13029"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13537"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13028"},{"issue":"13","key":"e_1_2_11_13_1","first-page":"3989","article-title":"Cell Fusion Following Photoreceptor Transplantation Into the Non\u2010Degenerate Retina","volume":"55","author":"Singh M. S.","year":"2014","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.04.004"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2023.09.005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010021\u201002539\u20108"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.09.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.054"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.09.011"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.48.9.856"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017204\u20105"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3791\/65448"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-84858-7"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010933404324"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2020.5743"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098587"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9437468"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xops.2023.100319"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/SCS.0000000000008946"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T23:21:48Z","timestamp":1766704908000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/cts.70420"],"URL":"https:\/\/doi.org\/10.1111\/cts.70420","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"type":"print","value":"1752-8054"},{"type":"electronic","value":"1752-8062"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70420"}}