{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:21:12Z","timestamp":1762431672632,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["43200004"],"award-info":[{"award-number":["43200004"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["TA-GT-0715-0665-LUMC"],"award-info":[{"award-number":["TA-GT-0715-0665-LUMC"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leiden Regenerative Medicine Platform","award":["2018-Project-B"],"award-info":[{"award-number":["2018-Project-B"]}]},{"name":"Rotterdamse Stichting Blindenbelangen and Landelijke Stichting voor Blinden en Slechtzienden","award":["Uitzicht-2018-6"],"award-info":[{"award-number":["Uitzicht-2018-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Variations in the Crumbs homolog-1 (CRB1) gene are associated with a wide variety of autosomal recessive retinal dystrophies, including early onset retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). CRB1 belongs to the Crumbs family, which in mammals includes CRB2 and CRB3. Here, we studied the specific roles of CRB2 in rod photoreceptor cells and whether ablation of CRB2 in rods exacerbates the Crb1-disease. Therefore, we assessed the morphological, retinal, and visual functional consequences of specific ablation of CRB2 from rods with or without concomitant loss of CRB1. Our data demonstrated that loss of CRB2 in mature rods resulted in RP. The retina showed gliosis and disruption of the subapical region and adherens junctions at the outer limiting membrane. Rods were lost at the peripheral and central superior retina, while gross retinal lamination was preserved. Rod function as measured by electroretinography was impaired in adult mice. Additional loss of CRB1 exacerbated the retinal phenotype leading to an early reduction of the dark-adapted rod photoreceptor a-wave and reduced contrast sensitivity from 3-months-of-age, as measured by optokinetic tracking reflex (OKT) behavior testing. The data suggest that CRB2 present in rods is required to prevent photoreceptor degeneration and vision loss.<\/jats:p>","DOI":"10.3390\/ijms20174069","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T11:19:06Z","timestamp":1566386346000},"page":"4069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["CRB2 Loss in Rod Photoreceptors Is Associated with Progressive Loss of Retinal Contrast Sensitivity"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-5701","authenticated-orcid":false,"given":"C. Henrique","family":"Alves","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9756-8898","authenticated-orcid":false,"given":"Nanda","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4779-099X","authenticated-orcid":false,"given":"Aat A.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Cell &amp; Chemical Biology, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham J.","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Cell &amp; Chemical Biology, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-1094","authenticated-orcid":false,"given":"Carolina R.","family":"Jost","sequence":"additional","affiliation":[{"name":"Department of Cell &amp; Chemical Biology, Leiden University Medical Center (LUMC), 2300 RC Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0099-460X","authenticated-orcid":false,"given":"Jan","family":"Wijnholds","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands"},{"name":"Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/0092-8674(90)90189-L","article-title":"Crumbs encodes an EGF-like protein expressed on apical membranes of Drosophila epithelial cells and required for organization of epithelia","volume":"61","author":"Tepass","year":"1990","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.preteyeres.2014.01.001","article-title":"The CRB1 and adherens junction complex proteins in retinal development and maintenance","volume":"40","author":"Alves","year":"2014","journal-title":"Prog. 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