{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:18:57Z","timestamp":1790705937393,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation Fighting Blindness (USA)"},{"name":"Moorfields Eye Charity (UK)"},{"name":"RetinaUK (UK)"},{"name":"Fight for Sight (UK)"},{"name":"Wellcome Trust (UK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The photoreceptor outer segment is a highly specialized primary cilium that is essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A&gt;G in CEP290, there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290-related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids by modulating the expression of rhodopsin and by targeting cilia and synaptic plasticity pathways. This work sheds light on the mechanism of action of eupatilin and supports its potential as a variant-independent approach for CEP290-associated ciliopathies.<\/jats:p>","DOI":"10.3390\/cells12121575","type":"journal-article","created":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T02:28:45Z","timestamp":1686104925000},"page":"1575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-4931","authenticated-orcid":false,"given":"Julio C.","family":"Corral-Serrano","sequence":"first","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E.","family":"Sladen","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1946-7351","authenticated-orcid":false,"given":"Daniele","family":"Ottaviani","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"},{"name":"Department of Biology, University of Padova, Padova, 35122 Padova PD, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia F.","family":"Rezek","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Jovanovic","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"van der Spuy","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8533-2789","authenticated-orcid":false,"given":"Brian C.","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B, Rockledge Drive, Montgomery County, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Cheetham","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/ng1786","article-title":"The Centrosomal Protein Nephrocystin-6 Is Mutated in Joubert Syndrome and Activates Transcription Factor ATF4","volume":"38","author":"Sayer","year":"2006","journal-title":"Nat. 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