{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:51:19Z","timestamp":1768697479656,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T00:00:00Z","timestamp":1584748800000},"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":["R01 EY029341"],"award-info":[{"award-number":["R01 EY029341"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY003039"],"award-info":[{"award-number":["P30 EY003039"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Patients with certain defects in the dehydrodolichyl diphosphate synthase (DHDDS) gene (RP59; OMIM #613861) exhibit classic symptoms of retinitis pigmentosa, as well as macular changes, suggestive of retinal pigment epithelium (RPE) involvement. The DHDDS enzyme is ubiquitously required for several pathways of protein glycosylation. We wish to understand the basis for selective ocular pathology associated with certain DHDDS mutations and the contribution of specific ocular cell types to the pathology of mutant Dhdds-mediated retinal degeneration. To circumvent embryonic lethality associated with Dhdds knockout, we generated a Cre-dependent knockout allele of murine Dhdds (Dhddsflx\/flx). We used targeted Cre expression to study the importance of the enzyme in the RPE. Structural alterations of the RPE and retina including reduction in outer retinal thickness, cell layer disruption, and increased RPE hyper-reflectivity were apparent at one postnatal month. At three months, RPE and photoreceptor disruption was observed non-uniformly across the retina as well as RPE transmigration into the photoreceptor layer, external limiting membrane descent towards the RPE, and patchy loss of photoreceptors. Functional loss measured by electroretinography was consistent with structural loss showing scotopic a- and b-wave reductions of 83% and 77%, respectively, at three months. These results indicate that RPE dysfunction contributes to DHDDS mutation-mediated pathology and suggests a more complicated disease mechanism than simply disruption of glycosylation.<\/jats:p>","DOI":"10.3390\/cells9030771","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T13:04:04Z","timestamp":1585055044000},"page":"771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Selective Ablation of Dehydrodolichyl Diphosphate Synthase in Murine Retinal Pigment Epithelium (RPE) Causes RPE Atrophy and Retinal Degeneration"],"prefix":"10.3390","volume":"9","author":[{"given":"Marci L.","family":"DeRamus","sequence":"first","affiliation":[{"name":"Department of Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-1051","authenticated-orcid":false,"given":"Sriganesh Ramachandra","family":"Rao","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Biochemistry, State University of New York-University at Buffalo, Buffalo, NY 14209, USA; and Research Service, VA Western NY Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyril","family":"Nyankerh","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delores","family":"Stacks","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy W.","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2557-142X","authenticated-orcid":false,"given":"Steven J.","family":"Fliesler","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Biochemistry, State University of New York-University at Buffalo, Buffalo, NY 14209, USA; and Research Service, VA Western NY Healthcare System, Buffalo, NY 14215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8464-9303","authenticated-orcid":false,"given":"Steven J.","family":"Pittler","sequence":"additional","affiliation":[{"name":"Department of Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/343364a0","article-title":"A point mutation of the rhodopsin gene in one form of retinitis pigmentosa","volume":"343","author":"Dryja","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1083\/jcb.49.3.664","article-title":"The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat","volume":"49","author":"Bok","year":"1971","journal-title":"J. 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