{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:45:59Z","timestamp":1791978359967,"version":"4.4.0"},"reference-count":97,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY028561"],"award-info":[{"award-number":["R01EY028561"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY011996"],"award-info":[{"award-number":["R01EY011996"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA034196"],"award-info":[{"award-number":["P30CA034196"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30EY025585"],"award-info":[{"award-number":["P30EY025585"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Veterans Administration","award":["BX005233"],"award-info":[{"award-number":["BX005233"]}]},{"name":"Edward N. and Della L. Thome Memorial Foundation Awards Program in Age-Related Macular Degeneration","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer blood\u2013retinal barrier. Characterizing these transporters and their role in retinal homeostasis may provide insights into ocular function and disease. Here, we describe RPE defects in tvrm77 mice, which exhibit hypopigmented patches in the central retina. Mapping and nucleotide sequencing of tvrm77 mice revealed a disrupted 5\u2019 splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. Slc4a5 expression was reduced 19.7-fold in tvrm77 RPE relative to controls, and alternative splice variants were detected. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells and in apical and basal membranes. Fundus imaging, optical coherence tomography, microscopy, and electroretinography (ERG) of tvrm77 mice revealed retinal detachment, hypopigmented patches corresponding to neovascular lesions, and retinal folds. Detachment worsened and outer nuclear layer thickness decreased with age. ERG a- and b-wave response amplitudes were initially normal but declined in older mice. The direct current ERG fast oscillation and light peak were reduced in amplitude at all ages, whereas other RPE-associated responses were unaffected. These results link a new Slc4a5 mutation to subretinal fluid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer blood\u2013retinal barrier.<\/jats:p>","DOI":"10.3390\/ijms23042220","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T20:25:45Z","timestamp":1645129545000},"page":"2220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction"],"prefix":"10.3390","volume":"23","author":[{"given":"Gayle B.","family":"Collin","sequence":"first","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Shi","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-8930","authenticated-orcid":false,"given":"Minzhong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA"},{"name":"Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurten","family":"Akturk","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy R.","family":"Charette","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian F.","family":"Hyde","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia M.","family":"Weatherly","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Pera","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen K.","family":"Naggert","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal S.","family":"Peachey","sequence":"additional","affiliation":[{"name":"Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA"},{"name":"Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA"},{"name":"Research Service, Louis Stokes Cleveland VA Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-5945","authenticated-orcid":false,"given":"Patsy M.","family":"Nishina","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9017-6066","authenticated-orcid":false,"given":"Mark P.","family":"Krebs","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/978-1-4614-4711-5_3","article-title":"The blood-retina barrier: Tight junctions and barrier modulation","volume":"763","author":"Campbell","year":"2012","journal-title":"Adv. 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