{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:40:21Z","timestamp":1791826821314,"version":"4.3.4"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["EY011373"],"award-info":[{"award-number":["EY011373"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Visual Science Training","award":["EY007157"],"award-info":[{"award-number":["EY007157"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A major cause for childhood blindness worldwide is attributed to nutritional vitamin A deficiency. Surprisingly, the molecular basis of the ensuing retinal degeneration has not been well defined. Abundant expression of the retinoid transporter STRA6 in the retinal pigment epithelium (RPE) and homeostatic blood levels of retinol-binding protein delay vitamin A deprivation of the mouse eyes. Hence, genetic dissection of STRA6 makes mice susceptible to nutritional manipulation of ocular retinoid status. We performed RNA-seq analyses and complemented the data with tests of visual physiology, ocular morphology, and retinoid biochemistry to compare eyes with different vitamin A status. Mild ocular vitamin A deficiency decreased transcripts of photoreceptor transduction pathway-related genes and increased transcripts of oxidative stress pathways. The response was associated with impaired visual sensitivity and an accumulation of fluorescent debris in the retina. Severe vitamin A deficiency did not only impair visual perception but also decreased transcripts of genes encoding cell adhesion and cellular junction proteins. This response altered cell morphology, resulted in significant changes in transport pathways of small molecules, and compromised the barrier function of the RPE. Together, our analyses characterize the molecular events underlying nutritional blindness in a novel mouse model and indicate that breakdown of the outer blood\u2013retinal barrier contributes to retinal degeneration and photoreceptor cell death in severe vitamin A deficiency.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad167","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T16:09:46Z","timestamp":1684512586000},"source":"Crossref","is-referenced-by-count":13,"title":["Vitamin A deficiency compromises the barrier function of the retinal pigment epithelium"],"prefix":"10.1093","volume":"2","author":[{"given":"Jean","family":"Moon","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Case Western Reserve University , Cleveland, OH 44106 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University , Cleveland, OH 44106 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7677-7412","authenticated-orcid":false,"given":"Eckhard","family":"Jankowsky","sequence":"additional","affiliation":[{"name":"Center for RNA Science and Therapeutics, School of Medicine, Case Western Reserve University , Cleveland, OH 44106 , USA"},{"name":"Department of Biochemistry, School of Medicine, Case Western Reserve University , Cleveland, OH 44106 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-2143","authenticated-orcid":false,"given":"Johannes","family":"von Lintig","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Case Western Reserve University , Cleveland, OH 44106 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"2023073115261149200_pgad167-B1","doi-asserted-by":"crossref","DOI":"10.1016\/j.preteyeres.2020.100864","article-title":"Molecular components affecting ocular carotenoid and retinoid homeostasis","volume":"80","author":"von Lintig","year":"2021","journal-title":"Prog Retin Eye Res"},{"key":"2023073115261149200_pgad167-B2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.cell.2009.09.029","article-title":"Phototransduction motifs and variations","volume":"139","author":"Yau","year":"2009","journal-title":"Cell"},{"key":"2023073115261149200_pgad167-B3","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1096\/fasebj.10.9.8801176","article-title":"A decade of molecular biology of retinoic acid receptors","volume":"10","author":"Chambon","year":"1996","journal-title":"FASEB J"},{"key":"2023073115261149200_pgad167-B4","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1126\/science.294.5548.1866","article-title":"Nuclear receptors and lipid physiology: opening the X-files","volume":"294","author":"Chawla","year":"2001","journal-title":"Science"},{"key":"2023073115261149200_pgad167-B5","doi-asserted-by":"crossref","first-page":"322","DOI":"10.3390\/cells11030322","article-title":"Towards a better vision of retinoic acid signaling during eye development","volume":"11","author":"Duester","year":"2022","journal-title":"Cells"},{"key":"2023073115261149200_pgad167-B6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/978-94-024-0945-1_4","article-title":"Vitamin A absorption, storage and mobilization","volume":"81","author":"Blaner","year":"2016","journal-title":"Subcell Biochem"},{"key":"2023073115261149200_pgad167-B7","doi-asserted-by":"crossref","first-page":"16559","DOI":"10.1016\/S0021-9258(19)89425-5","article-title":"Lipoprotein lipase hydrolysis of retinyl ester. 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