Feasibility of cell-based therapy combined with descemetorhexis for treating Fuchs endothelial corneal dystrophy in rabbit model
Corneal transparency is maintained by the corneal endothelium through its pump and barrier function. Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-b...
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| creator | Okumura, Naoki Matsumoto, Daiki Fukui, Yuya Teramoto, Masataka Imai, Hirofumi Kurosawa, Tetta Shimada, Tomoki Kruse, Friedrich Schlötzer-Schrehardt, Ursula Kinoshita, Shigeru Koizumi, Noriko |
| description | Corneal transparency is maintained by the corneal endothelium through its pump and barrier function. Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet's membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet's membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet's membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet's membrane removal) and on the intact peripheral Descemet's membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet's membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet's membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet's membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD. |
| doi_str_mv | 10.1371/journal.pone.0191306 |
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Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet's membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet's membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet's membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet's membrane removal) and on the intact peripheral Descemet's membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet's membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet's membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet's membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0191306</identifier><identifier>PMID: 29338061</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Anterior chamber ; Biology and Life Sciences ; Biomedical engineering ; Cell density ; Collagen ; Cornea ; Corneal dystrophy ; Corneal transplantation ; Dystrophy ; Edema ; Endothelial cells ; Endothelium ; Engineering ; Engineering and Technology ; Extracellular matrix ; Feasibility studies ; Injection ; Medical research ; Medicine and Health Sciences ; Patients ; Research and Analysis Methods ; Restoration ; Stroma ; Studies ; Therapy ; Thickening ; Transparency ; Turnover time ; Visual perception ; Water flow</subject><ispartof>PloS one, 2018-01, Vol.13 (1), p.e0191306-e0191306</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Okumura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Therefore, we used a rabbit model to evaluate the feasibility of Descemet's membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet's membrane removal) and on the intact peripheral Descemet's membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet's membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet's membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet's membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.</description><subject>Analysis</subject><subject>Anterior chamber</subject><subject>Biology and Life Sciences</subject><subject>Biomedical engineering</subject><subject>Cell density</subject><subject>Collagen</subject><subject>Cornea</subject><subject>Corneal dystrophy</subject><subject>Corneal transplantation</subject><subject>Dystrophy</subject><subject>Edema</subject><subject>Endothelial cells</subject><subject>Endothelium</subject><subject>Engineering</subject><subject>Engineering and Technology</subject><subject>Extracellular matrix</subject><subject>Feasibility studies</subject><subject>Injection</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Patients</subject><subject>Research and Analysis 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of cell-based therapy combined with descemetorhexis for treating Fuchs endothelial corneal dystrophy in rabbit model</title><author>Okumura, Naoki ; Matsumoto, Daiki ; Fukui, Yuya ; Teramoto, Masataka ; Imai, Hirofumi ; Kurosawa, Tetta ; Shimada, Tomoki ; Kruse, Friedrich ; Schlötzer-Schrehardt, Ursula ; Kinoshita, Shigeru ; Koizumi, Noriko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-39b6607a8a5542608e796c9cd473213121d6a1d533239fc039fe5bcc44e17a353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Analysis</topic><topic>Anterior chamber</topic><topic>Biology and Life Sciences</topic><topic>Biomedical engineering</topic><topic>Cell density</topic><topic>Collagen</topic><topic>Cornea</topic><topic>Corneal dystrophy</topic><topic>Corneal transplantation</topic><topic>Dystrophy</topic><topic>Edema</topic><topic>Endothelial 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Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet's membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet's membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet's membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet's membrane removal) and on the intact peripheral Descemet's membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet's membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet's membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet's membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29338061</pmid><doi>10.1371/journal.pone.0191306</doi><tpages>e0191306</tpages><orcidid>https://orcid.org/0000-0002-6940-1334</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2018-01, Vol.13 (1), p.e0191306-e0191306 |
| issn | 1932-6203 1932-6203 |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Anterior chamber Biology and Life Sciences Biomedical engineering Cell density Collagen Cornea Corneal dystrophy Corneal transplantation Dystrophy Edema Endothelial cells Endothelium Engineering Engineering and Technology Extracellular matrix Feasibility studies Injection Medical research Medicine and Health Sciences Patients Research and Analysis Methods Restoration Stroma Studies Therapy Thickening Transparency Turnover time Visual perception Water flow |
| title | Feasibility of cell-based therapy combined with descemetorhexis for treating Fuchs endothelial corneal dystrophy in rabbit model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T18%3A36%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Feasibility%20of%20cell-based%20therapy%20combined%20with%20descemetorhexis%20for%20treating%20Fuchs%20endothelial%20corneal%20dystrophy%20in%20rabbit%20model&rft.jtitle=PloS%20one&rft.au=Okumura,%20Naoki&rft.date=2018-01-16&rft.volume=13&rft.issue=1&rft.spage=e0191306&rft.epage=e0191306&rft.pages=e0191306-e0191306&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0191306&rft_dat=%3Cgale_plos_%3EA523353993%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1988112363&rft_id=info:pmid/29338061&rft_galeid=A523353993&rft_doaj_id=oai_doaj_org_article_6019033f088a4667b41885d2eaf617dc&rfr_iscdi=true |