{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:35:08Z","timestamp":1790501708168,"version":"4.1.0"},"reference-count":55,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerische Nationalfonds","doi-asserted-by":"crossref","award":["31003A_173083"],"award-info":[{"award-number":["31003A_173083"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY028121"],"award-info":[{"award-number":["EY028121"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY020551"],"award-info":[{"award-number":["EY020551"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Robert und Rosa Pulfer Stiftung"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,10,20]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>RLBP1<\/jats:italic>\n                    gene encodes the 36 kDa cellular retinaldehyde-binding protein, CRALBP, a soluble retinoid carrier, in the visual cycle of the eyes. Mutations in\n                    <jats:italic>RLBP1<\/jats:italic>\n                    are associated with recessively inherited clinical phenotypes, including Bothnia dystrophy, retinitis pigmentosa, retinitis punctata albescens, fundus albipunctatus, and Newfoundland rod\u2013cone dystrophy. However, the etiology of these retinal disorders is not well understood. Here, we generated homologous zebrafish models to bridge this knowledge gap. Duplication of the\n                    <jats:italic>rlbp1<\/jats:italic>\n                    gene in zebrafish and cell-specific expression of the paralogs\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    in the retinal pigment epithelium and\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    in M\u00fcller glial cells allowed us to create intrinsically cell type-specific knockout fish lines. Using\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    and\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    single and double mutants, we investigated the pathological effects on visual function. Our analyses revealed that\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    was essential for cone photoreceptor function and chromophore metabolism in the fish eyes.\n                    <jats:italic>rlbp1a-<\/jats:italic>\n                    mutant fish displayed reduced chromophore levels and attenuated cone photoreceptor responses to light stimuli. They accumulated 11-\n                    <jats:italic>cis<\/jats:italic>\n                    and all-\n                    <jats:italic>trans<\/jats:italic>\n                    -retinyl esters which displayed as enlarged lipid droplets in the RPE reminiscent of the subretinal yellow-white lesions in patients with\n                    <jats:italic>RLBP1<\/jats:italic>\n                    mutations. During aging, these fish developed retinal thinning and cone and rod photoreceptor dystrophy. In contrast,\n                    <jats:italic>rlbp1b<\/jats:italic>\n                    mutants did not display impaired vision. The double mutant essentially replicated the phenotype of the\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    single mutant. Together, our study showed that the\n                    <jats:italic>rlbp1a<\/jats:italic>\n                    zebrafish mutant recapitulated many features of human blinding diseases caused by\n                    <jats:italic>RLBP1<\/jats:italic>\n                    mutations and provided novel insights into the pathways for chromophore regeneration of cone photoreceptors.\n                  <\/jats:p>","DOI":"10.7554\/elife.71473","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T08:26:51Z","timestamp":1634718411000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.71473","source":"Crossref","is-referenced-by-count":27,"title":["Disturbed retinoid metabolism upon loss of rlbp1a impairs cone function and leads to subretinal lipid deposits and photoreceptor degeneration in the zebrafish retina"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6194-4695","authenticated-orcid":true,"given":"Domino K","family":"Schlegel","sequence":"first","affiliation":[{"name":"Department of Molecular Life Sciences, University of Zurich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasagan","family":"Ramkumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Case Western Reserve University","place":["Cleveland, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"von Lintig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Case Western Reserve University","place":["Cleveland, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9615-480X","authenticated-orcid":true,"given":"Stephan CF","family":"Neuhauss","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, University of Zurich","place":["Z\u00fcrich, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1096\/fj.14-261693","article-title":"The role of 11-cis-retinyl esters in vertebrate cone vision","volume":"29","author":"Babino","year":"2015","journal-title":"FASEB Journal"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/dvdy.1188","article-title":"Rod contributions to the electroretinogram of the dark-adapted developing zebrafish","volume":"222","author":"Bilotta","year":"2001","journal-title":"Developmental Dynamics"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1002\/cne.902240110","article-title":"The development of photoreceptors in the zebrafish, brachy Danio rerio. 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