In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy
Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in orde...
Saved in:
| Published in | Frontiers in immunology Vol. 12; p. 757607 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Media S.A
02.11.2021
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.
A total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.
The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.
This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach. |
|---|---|
| AbstractList | BackgroundRetinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.MethodsA total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.ResultsThe in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.ConclusionThis study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach. Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR. A total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease. The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR. This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach. Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.BackgroundRetinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease proliferative diabetic retinopathy (PDR). The aim of this study was to characterize the molecular, cellular and immunological features of RNV in order to unravel potential novel drug treatments for PDR.A total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.MethodsA total of 43 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Immune cells of the vitreous body, also known as hyalocytes, were isolated from patients with PDR by flow cytometry, cultivated and characterized by immunohistochemistry. A bioinformatical drug repurposing approach was applied in order to identify novel potential drug options for end-stage diabetic retinopathy disease.The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.ResultsThe in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential immunomodulatory drug option for future treatment of PDR.This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach.ConclusionThis study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and their modulation as a novel possible clinical approach. |
| Author | Stahl, Andreas Boneva, Stefaniya Konstantinova Busch, Martin Schlunck, Günther Hajdú, Rozina Ida Lange, Clemens A. K. Faatz, Henrik Laich, Yannik Lommatzsch, Albrecht Prinz, Gabriele Böhringer, Daniel Agostini, Hansjürgen Wolf, Julian Bengsch, Bertram Bucher, Felicitas Schlecht, Anja Salié, Henrike Killmer, Saskia |
| AuthorAffiliation | 3 Department of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Faculty of Medicine, University Medical Center Freiburg , Freiburg , Germany 5 St. Franziskus Eye Center , Münster , Germany 6 Department of Ophthalmology, University Medical Center Greifswald , Greifswald , Germany 1 Eye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg , Freiburg , Germany 2 Department of Ophthalmology, Semmelweis University , Budapest , Hungary 4 Institute for Anatomy and Cell Biology, Julius-Maximilians-University Würzburg , Würzburg , Germany |
| AuthorAffiliation_xml | – name: 2 Department of Ophthalmology, Semmelweis University , Budapest , Hungary – name: 4 Institute for Anatomy and Cell Biology, Julius-Maximilians-University Würzburg , Würzburg , Germany – name: 1 Eye Center, Medical Center, Faculty of Medicine, University Medical Center Freiburg , Freiburg , Germany – name: 6 Department of Ophthalmology, University Medical Center Greifswald , Greifswald , Germany – name: 5 St. Franziskus Eye Center , Münster , Germany – name: 3 Department of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Disease, Faculty of Medicine, University Medical Center Freiburg , Freiburg , Germany |
| Author_xml | – sequence: 1 givenname: Stefaniya Konstantinova surname: Boneva fullname: Boneva, Stefaniya Konstantinova – sequence: 2 givenname: Julian surname: Wolf fullname: Wolf, Julian – sequence: 3 givenname: Rozina Ida surname: Hajdú fullname: Hajdú, Rozina Ida – sequence: 4 givenname: Gabriele surname: Prinz fullname: Prinz, Gabriele – sequence: 5 givenname: Henrike surname: Salié fullname: Salié, Henrike – sequence: 6 givenname: Anja surname: Schlecht fullname: Schlecht, Anja – sequence: 7 givenname: Saskia surname: Killmer fullname: Killmer, Saskia – sequence: 8 givenname: Yannik surname: Laich fullname: Laich, Yannik – sequence: 9 givenname: Henrik surname: Faatz fullname: Faatz, Henrik – sequence: 10 givenname: Albrecht surname: Lommatzsch fullname: Lommatzsch, Albrecht – sequence: 11 givenname: Martin surname: Busch fullname: Busch, Martin – sequence: 12 givenname: Felicitas surname: Bucher fullname: Bucher, Felicitas – sequence: 13 givenname: Andreas surname: Stahl fullname: Stahl, Andreas – sequence: 14 givenname: Daniel surname: Böhringer fullname: Böhringer, Daniel – sequence: 15 givenname: Bertram surname: Bengsch fullname: Bengsch, Bertram – sequence: 16 givenname: Günther surname: Schlunck fullname: Schlunck, Günther – sequence: 17 givenname: Hansjürgen surname: Agostini fullname: Agostini, Hansjürgen – sequence: 18 givenname: Clemens A. K. surname: Lange fullname: Lange, Clemens A. K. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34795670$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9Uk1v1DAQjVARLaU_gAvykUsWx19JLkhoC3SlLqBSzpbjjHddJfFiOyuFH8TvxLspVcsBH2xrZt6bmTfzMjsZ3ABZ9rrAC0qr-p2xfT8uCCbFouSlwOWz7KwQguWUEHby6H-aXYRwh9NhNaWUv8hOKStrLkp8lv1eDfkl7OIWrV0HeuyUR8ut8kpH8PaXitYNyBn0Bdxehdm_hr7xaoCAvo-bDYQYkEI3CY6M8-hqUp3TU4Q8unw9OWMb75pOhYhuEyq01hjwMEQ7k9sBffOus8mYDHtAl1Y1EK1GN-ke3E7F7fQqe25UF-Di_j3Pfnz6eLu8yq-_fl4tP1znmtMi5hXTUKcuNbSkLjQDygUH1mCqqVFUlApaDi3WSRvFTFFhxkTLkxaKANQNPc9WM2_r1J3cedsrP0mnrDwanN9I5VNtHUiDCRYlcFxXNTOENpoKgEoIQYEIThPX-5lrNzY9tDq17FX3hPSpZ7BbuXF7WfGakuJA8PaewLufY9JZ9jZo6LqkvRuDJLyuUwslJSn0zeNcD0n-DjoFFHOA9i4ED-YhpMDysE_yuE_ysE9y3qeEKf_BaBuPQ0vl2u4_yD-hE9Wc |
| CitedBy_id | crossref_primary_10_3390_ijms222413318 crossref_primary_10_22141_2224_0721_19_5_2023_1296 crossref_primary_10_3389_fimmu_2022_855466 crossref_primary_10_1002_ctm2_1751 crossref_primary_10_1007_s00109_024_02437_5 crossref_primary_10_3389_fendo_2022_869519 crossref_primary_10_1167_iovs_63_5_17 crossref_primary_10_3390_biomedicines10040840 crossref_primary_10_1007_s00417_024_06448_3 crossref_primary_10_1186_s12974_025_03391_w crossref_primary_10_3390_ijms241713510 crossref_primary_10_1016_j_pdpdt_2023_103530 crossref_primary_10_1080_17469899_2022_2100764 crossref_primary_10_1111_aos_16755 crossref_primary_10_1080_17469899_2022_2100762 crossref_primary_10_1080_17469899_2022_2100763 crossref_primary_10_1097_IAE_0000000000004100 crossref_primary_10_3390_ijms23169181 crossref_primary_10_1007_s13577_025_01182_2 crossref_primary_10_1080_09273948_2022_2080719 crossref_primary_10_1016_j_pdpdt_2023_103929 crossref_primary_10_3389_fimmu_2022_987836 crossref_primary_10_1186_s12974_024_03291_5 crossref_primary_10_1016_j_survophthal_2024_10_001 crossref_primary_10_1016_j_ygeno_2022_110286 crossref_primary_10_1167_iovs_64_15_46 crossref_primary_10_1186_s12974_024_03110_x crossref_primary_10_3389_fendo_2022_841813 crossref_primary_10_1167_iovs_63_3_9 crossref_primary_10_3389_fmolb_2023_1235428 crossref_primary_10_3390_cells13221837 |
| Cites_doi | 10.1186/1742-2094-8-120 10.1016/j.cmet.2018.11.014 10.1093/bioinformatics/bts635 10.1126/scitranslmed.3001318 10.1007/s00441-019-03166-9 10.1186/gb-2006-7-10-r100 10.1016/S0140-6736(09)62124-3 10.1016/j.cell.2015.05.047 10.1186/s13059-014-0550-8 10.3389/fimmu.2020.567274 10.1038/s41421-020-0153-3 10.1007/978-3-319-24277-4 10.1001/jama.2015.15217 10.1167/iovs.13-13634 10.1001/archopht.126.12.1740 10.1002/glia.23810 10.1186/s13059-017-1349-1 10.1126/science.1132939 10.1007/s11892-017-0913-0 10.1038/s41598-020-72864-0 10.1002/path.2277 10.1093/bioinformatics/btw313 10.1016/j.ajo.2011.02.014 10.1038/s41467-019-13055-y 10.1159/000491726 10.1016/S0161-6420(90)32486-7 10.1167/iovs.16-19798 10.1093/nar/gkaa434 10.24966/OCR-8887/100002 10.1038/nmeth.4391 10.1016/S0161-6420(78)35693-1 10.1016/j.ophtha.2016.02.022 10.1016/S0161-6420(85)34015-0 10.1038/cddis.2016.402 10.1159/000331418 10.1016/j.preteyeres.2015.08.001 10.1016/j.immuni.2021.06.002 10.1109/ISBI.2011.5872394 10.1007/s12064-012-0162-3 10.1186/1756-9966-29-71 10.3109/02713683.2010.514659 10.1093/bioinformatics/btt656 10.1093/nar/gkaa942 10.1186/s12886-021-02099-8 10.1038/sj.bjc.6605538 10.1080/08820538.2016.1228397 10.1002/ijc.23450 10.5551/jat.E711 10.1001/archophthalmol.2007.65 10.1083/jcb.200506152 10.1167/iovs.07-0956 10.1016/j.phrs.2018.05.002 10.1016/j.ebiom.2018.11.029 10.1089/omi.2011.0118 10.18240/ijo.2017.12.18 10.1517/13543784.2012.681043 10.1136/bjophthalmol-2014-305321 10.1167/iovs.03-1330 10.1136/bjo.76.9.550 10.1073/pnas.0804054105 |
| ContentType | Journal Article |
| Copyright | Copyright © 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange. Copyright © 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange |
| Copyright_xml | – notice: Copyright © 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange. – notice: Copyright © 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 5PM DOA |
| DOI | 10.3389/fimmu.2021.757607 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Biology |
| EISSN | 1664-3224 |
| ExternalDocumentID | oai_doaj_org_article_f02067e509894f23bc36ee86663e2653 PMC8593213 34795670 10_3389_fimmu_2021_757607 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | 53G 5VS 9T4 AAFWJ AAKDD AAYXX ACGFO ACGFS ACXDI ADBBV ADRAZ AENEX AFPKN ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BCNDV CITATION DIK EBS EMOBN GROUPED_DOAJ GX1 HYE KQ8 M48 M~E OK1 PGMZT RNS RPM CGR CUY CVF ECM EIF IAO IEA IHR IHW IPNFZ NPM RIG 7X8 5PM |
| ID | FETCH-LOGICAL-c531t-84ce9493ced291c4e3565e4b03c3fa367aed5ed0c664a4f180446d5956a2ee9b3 |
| IEDL.DBID | M48 |
| ISSN | 1664-3224 |
| IngestDate | Wed Aug 27 01:23:18 EDT 2025 Thu Aug 21 18:21:10 EDT 2025 Fri Jul 11 15:19:50 EDT 2025 Thu Jan 02 22:55:22 EST 2025 Thu Apr 24 23:05:32 EDT 2025 Tue Jul 01 00:53:24 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | RNA sequencing Imaging Mass Cytometry proliferative diabetic retinopathy (PDR) transdifferentiation retinal neovascularization (RNV) myofibroblasts hyalocytes |
| Language | English |
| License | Copyright © 2021 Boneva, Wolf, Hajdú, Prinz, Salié, Schlecht, Killmer, Laich, Faatz, Lommatzsch, Busch, Bucher, Stahl, Böhringer, Bengsch, Schlunck, Agostini and Lange. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c531t-84ce9493ced291c4e3565e4b03c3fa367aed5ed0c664a4f180446d5956a2ee9b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Steven O’Reilly, STipe Therapeutics, Denmark This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology Reviewed by: Mohd Imtiaz Nawaz, King Saud University, Saudi Arabia; Sheik Pran Babu Sardar Pasha, University of California, Davis, United States; Ian Dixon, University of Manitoba, Canada |
| OpenAccessLink | http://journals.scholarsportal.info/openUrl.xqy?doi=10.3389/fimmu.2021.757607 |
| PMID | 34795670 |
| PQID | 2599180732 |
| PQPubID | 23479 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_f02067e509894f23bc36ee86663e2653 pubmedcentral_primary_oai_pubmedcentral_nih_gov_8593213 proquest_miscellaneous_2599180732 pubmed_primary_34795670 crossref_primary_10_3389_fimmu_2021_757607 crossref_citationtrail_10_3389_fimmu_2021_757607 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-11-02 |
| PublicationDateYYYYMMDD | 2021-11-02 |
| PublicationDate_xml | – month: 11 year: 2021 text: 2021-11-02 day: 02 |
| PublicationDecade | 2020 |
| PublicationPlace | Switzerland |
| PublicationPlace_xml | – name: Switzerland |
| PublicationTitle | Frontiers in immunology |
| PublicationTitleAlternate | Front Immunol |
| PublicationYear | 2021 |
| Publisher | Frontiers Media S.A |
| Publisher_xml | – name: Frontiers Media S.A |
| References | Wickham (B22) 2016 Schlecht (B31) 2021; 21 Tamaki (B12) 2016; 57 Aran (B25) 2017; 18 Wynn (B14) 2008; 214 Zhou (B62) 2018; 48 Lange (B3) 2012; 227 Olivares (B44) 2017; 17 Liao (B19) 2014; 30 Zhou (B28) 2020; 6 Patz (B41) 1978; 85 Watanabe (B46) 2009; 16 Liang (B49) 2010; 29 Love (B21) 2014; 15 Dobin (B18) 2013; 29 Schlunck (B39) 2008; 49 Gross (B6) 2015; 314 Belkina (B37) 2019; 10 Wolf (B17) 2020; 10 Kita (B60) 2008; 105 Sommer (B33) 2011 Fischer (B40) 2011; 8 Kowluru (B52) 2012; 21 Boneva (B9) 2020; 11 Walshe (B13) 1992; 76 Kobayashi (B55) 2015; 99 El Rami (B5) 2017; 32 Bhoopathi (B48) 2010; 102 Boeck (B15) 2020; 68 Lange (B2) 2011; 152 Sobeih (B47) 2014; 1 Das (B51) 1999; 40 Levine (B36) 2015; 162 Gu (B23) 2016; 32 Meng (B58) 2016; 7 Kim (B11) 2015; 21 Yu (B24) 2012; 16 Little (B59) 2018; 38 Zhou (B54) 2017; 10 Wang (B56) 2020; 380 Cheung (B1) 2010; 376 Sirota (B27) 2011; 3 de Rooij (B38) 2005; 171 Schapiro (B35) 2017; 14 Wells (B42) 2016; 123 Carpenter (B34) 2006; 7 Saaddine (B43) 2008; 126 Akiba (B7) 1990; 97 Urbančič (B53) 2014; 55 Lamb (B29) 2006; 313 Roy (B45) 2010; 35 Yunker (B50) 2008; 122 Jalili (B16) 2020; 48 Zeng (B57) 2008; 126 Blankenship (B8) 1985; 92 Wagner (B26) 2012; 131 Hirayama (B10) 2004; 45 Yao (B61) 2018; 133 Howe (B20) 2021; 49 Stitt (B4) 2016; 51 Damond (B32) 2019; 29 Schwabenland (B30) 2021; 54 |
| References_xml | – volume: 8 year: 2011 ident: B40 article-title: Activation of Retinal Microglia Rather Than Microglial Cell Density Correlates With Retinal Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy publication-title: J Neuroinflamm doi: 10.1186/1742-2094-8-120 – volume: 40 year: 1999 ident: B51 article-title: Human Diabetic Neovascular Membranes Contain High Levels of Urokinase and Metalloproteinase Enzymes publication-title: Invest Ophthalmol Vis Sci – volume: 29 start-page: 755 year: 2019 ident: B32 article-title: A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry publication-title: Cell Metab doi: 10.1016/j.cmet.2018.11.014 – volume: 29 start-page: 15 year: 2013 ident: B18 article-title: STAR: Ultrafast Universal RNA-Seq Aligner publication-title: Bioinformatics doi: 10.1093/bioinformatics/bts635 – volume: 3 start-page: 96ra77 year: 2011 ident: B27 article-title: Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data publication-title: Sci Transl Med doi: 10.1126/scitranslmed.3001318 – volume: 380 year: 2020 ident: B56 article-title: M2 Macrophages Promote Vasculogenesis During Retinal Neovascularization by Regulating Bone Marrow-Derived Cells via SDF-1/VEGF publication-title: Cell Tissue Res doi: 10.1007/s00441-019-03166-9 – volume: 7 start-page: R100 year: 2006 ident: B34 article-title: CellProfiler: Image Analysis Software for Identifying and Quantifying Cell Phenotypes publication-title: Genome Biol doi: 10.1186/gb-2006-7-10-r100 – volume: 376 year: 2010 ident: B1 article-title: Diabetic Retinopathy publication-title: Lancet doi: 10.1016/S0140-6736(09)62124-3 – volume: 162 year: 2015 ident: B36 article-title: Data-Driven Phenotypic Dissection of AML Reveals Progenitor-Like Cells That Correlate With Prognosis publication-title: Cell doi: 10.1016/j.cell.2015.05.047 – volume: 21 year: 2015 ident: B11 article-title: Characterization of Cells From Patient-Derived Fibrovascular Membranes in Proliferative Diabetic Retinopathy publication-title: Mol Vis – volume: 15 year: 2014 ident: B21 article-title: Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data With Deseq2 publication-title: Genome Biol doi: 10.1186/s13059-014-0550-8 – volume: 11 year: 2020 ident: B9 article-title: Transcriptional Profiling Uncovers Human Hyalocytes as a Unique Innate Immune Cell Population publication-title: Front Immunol doi: 10.3389/fimmu.2020.567274 – volume: 6 year: 2020 ident: B28 article-title: Network-Based Drug Repurposing for Novel Coronavirus 2019-Ncov/SARS-CoV-2 publication-title: Cell Discov doi: 10.1038/s41421-020-0153-3 – volume-title: Ggplot2: Elegant Graphics for Data Analysis year: 2016 ident: B22 doi: 10.1007/978-3-319-24277-4 – volume: 314 year: 2015 ident: B6 article-title: Panretinal Photocoagulation vs. Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial publication-title: JAMA doi: 10.1001/jama.2015.15217 – volume: 55 year: 2014 ident: B53 article-title: Epiretinal Membrane Inflammatory Cell Density Might Reflect the Activity of Proliferative Diabetic Retinopathy publication-title: Invest Ophthalmol Vis Sci doi: 10.1167/iovs.13-13634 – volume: 126 year: 2008 ident: B43 article-title: Projection of Diabetic Retinopathy and Other Major Eye Diseases Among People With Diabetes Mellitus: United States, 2005-2050 publication-title: Arch Ophthalmol doi: 10.1001/archopht.126.12.1740 – volume: 68 year: 2020 ident: B15 article-title: Temporospatial Distribution and Transcriptional Profile of Retinal Microglia in the Oxygen-Induced Retinopathy Mouse Model publication-title: Glia doi: 10.1002/glia.23810 – volume: 18 start-page: 220 year: 2017 ident: B25 article-title: Xcell: Digitally Portraying the Tissue Cellular Heterogeneity Landscape publication-title: Genome Biol doi: 10.1186/s13059-017-1349-1 – volume: 313 year: 2006 ident: B29 article-title: The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease publication-title: Science doi: 10.1126/science.1132939 – volume: 17 start-page: 93 year: 2017 ident: B44 article-title: Animal Models of Diabetic Retinopathy publication-title: Curr Diabetes Rep doi: 10.1007/s11892-017-0913-0 – volume: 10 start-page: 17022 year: 2020 ident: B17 article-title: Transcriptional Characterization of Conjunctival Melanoma Identifies the Cellular Tumor Microenvironment and Prognostic Gene Signatures publication-title: Sci Rep doi: 10.1038/s41598-020-72864-0 – volume: 214 start-page: 199 year: 2008 ident: B14 article-title: Cellular and Molecular Mechanisms of Fibrosis publication-title: J Pathol doi: 10.1002/path.2277 – volume: 32 year: 2016 ident: B23 article-title: Complex Heatmaps Reveal Patterns and Correlations in Multidimensional Genomic Data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btw313 – volume: 152 year: 2011 ident: B2 article-title: Intraocular Oxygen Distribution in Advanced Proliferative Diabetic Retinopathy publication-title: AmJOphthalmol doi: 10.1016/j.ajo.2011.02.014 – volume: 10 start-page: 5415 year: 2019 ident: B37 article-title: Automated Optimized Parameters for T-Distributed Stochastic Neighbor Embedding Improve Visualization and Analysis of Large Datasets publication-title: Nat Commun doi: 10.1038/s41467-019-13055-y – volume: 48 year: 2018 ident: B62 article-title: Imatinib Ameliorated Retinal Neovascularization by Suppressing PDGFR-α and PDGFR-β publication-title: Cell Physiol Biochem doi: 10.1159/000491726 – volume: 97 year: 1990 ident: B7 article-title: Posterior Vitreous Detachment and Neovascularization in Diabetic Retinopathy publication-title: Ophthalmology doi: 10.1016/S0161-6420(90)32486-7 – volume: 57 start-page: 4999 year: 2016 ident: B12 article-title: Fibrocytes and Fibrovascular Membrane Formation in Proliferative Diabetic Retinopathy publication-title: Invest Ophthalmol Vis Sci doi: 10.1167/iovs.16-19798 – volume: 48 year: 2020 ident: B16 article-title: The Galaxy Platform for Accessible, Reproducible and Collaborative Biomedical Analyses: 2020 Update publication-title: Nucleic Acids Res doi: 10.1093/nar/gkaa434 – volume: 1 start-page: 1 year: 2014 ident: B47 article-title: Deletion of SPARC Enhances Retinal Vaso-Obliteration in Mouse Model of Oxygen-Induced Retinopathy publication-title: HSOA J Ophthalmol Clin Res doi: 10.24966/OCR-8887/100002 – volume: 14 year: 2017 ident: B35 article-title: histoCAT: Analysis of Cell Phenotypes and Interactions in Multiplex Image Cytometry Data publication-title: Nat Methods doi: 10.1038/nmeth.4391 – volume: 85 start-page: 82 year: 1978 ident: B41 article-title: Photocoagulation Treatment of Proliferative Diabetic Retinopathy: The Second Report of Diabetic Retinopathy Study Findings publication-title: Ophthalmology doi: 10.1016/S0161-6420(78)35693-1 – volume: 123 year: 2016 ident: B42 article-title: Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema publication-title: Ophthalmology doi: 10.1016/j.ophtha.2016.02.022 – volume: 92 year: 1985 ident: B8 article-title: Long-Term Diabetic Vitrectomy Results publication-title: Ophthalmology doi: 10.1016/S0161-6420(85)34015-0 – volume: 7 start-page: e2495 year: 2016 ident: B58 article-title: Inflammatory Macrophages can Transdifferentiate Into Myofibroblasts During Renal Fibrosis publication-title: Cell Death Dis doi: 10.1038/cddis.2016.402 – volume: 227 year: 2012 ident: B3 article-title: Oxygen Sensing in Retinal Health and Disease publication-title: Ophthalmologica doi: 10.1159/000331418 – volume: 51 year: 2016 ident: B4 article-title: The Progress in Understanding and Treatment of Diabetic Retinopathy publication-title: Prog Retinal Eye Res doi: 10.1016/j.preteyeres.2015.08.001 – volume: 54 year: 2021 ident: B30 article-title: Deep Spatial Profiling of Human COVID-19 Brains Reveals Neuroinflammation With Distinct Microanatomical Microglia-T-Cell Interactions publication-title: Immunity doi: 10.1016/j.immuni.2021.06.002 – year: 2011 ident: B33 article-title: Ilastik: Interactive Learning and Segmentation Toolkit publication-title: IEEE Int Symposium Biomed Imaging: From Nano to Macro doi: 10.1109/ISBI.2011.5872394 – volume: 131 year: 2012 ident: B26 article-title: Measurement of mRNA Abundance Using RNA-Seq Data: RPKM Measure is Inconsistent Among Samples publication-title: Theory Biosci doi: 10.1007/s12064-012-0162-3 – volume: 29 year: 2010 ident: B49 article-title: Relationship and Prognostic Significance of SPARC and VEGF Protein Expression in Colon Cancer publication-title: J Exp Clin Cancer Res doi: 10.1186/1756-9966-29-71 – volume: 35 year: 2010 ident: B45 article-title: Vascular Basement Membrane Thickening in Diabetic Retinopathy publication-title: Curr Eye Res doi: 10.3109/02713683.2010.514659 – volume: 30 year: 2014 ident: B19 article-title: Featurecounts: An Efficient General Purpose Program for Assigning Sequence Reads to Genomic Features publication-title: Bioinformatics doi: 10.1093/bioinformatics/btt656 – volume: 49 year: 2021 ident: B20 article-title: Ensembl 2021 publication-title: Nucleic Acids Res doi: 10.1093/nar/gkaa942 – volume: 21 start-page: 338 year: 2021 ident: B31 article-title: Imaging Mass Cytometry for High-Dimensional Tissue Profiling in the Eye publication-title: BMC Ophthalmol doi: 10.1186/s12886-021-02099-8 – volume: 102 year: 2010 ident: B48 article-title: The Role of MMP-9 in the Anti-Angiogenic Effect of Secreted Protein Acidic and Rich in Cysteine publication-title: Br J Cancer doi: 10.1038/sj.bjc.6605538 – volume: 32 start-page: 67 year: 2017 ident: B5 article-title: Evidence-Based Treatment of Diabetic Retinopathy publication-title: Semin Ophthalmol doi: 10.1080/08820538.2016.1228397 – volume: 122 year: 2008 ident: B50 article-title: SPARC-Induced Increase in Glioma Matrix and Decrease in Vascularity are Associated With Reduced VEGF Expression and Secretion publication-title: Int J Cancer doi: 10.1002/ijc.23450 – volume: 16 start-page: 69 year: 2009 ident: B46 article-title: SPARC is a Major Secretory Gene Expressed and Involved in the Development of Proliferative Diabetic Retinopathy publication-title: JAT doi: 10.5551/jat.E711 – volume: 126 start-page: 227 year: 2008 ident: B57 article-title: Microglial Activation in Human Diabetic Retinopathy publication-title: Arch Ophthalmol doi: 10.1001/archophthalmol.2007.65 – volume: 171 year: 2005 ident: B38 article-title: Integrin-Dependent Actomyosin Contraction Regulates Epithelial Cell Scattering publication-title: J Cell Biol doi: 10.1083/jcb.200506152 – volume: 49 start-page: 262 year: 2008 ident: B39 article-title: Substrate Rigidity Modulates Cell–Matrix Interactions and Protein Expression in Human Trabecular Meshwork Cells publication-title: Invest Ophthalmol Vis Sci doi: 10.1167/iovs.07-0956 – volume: 133 year: 2018 ident: B61 article-title: Imatinib Prevents Lung Cancer Metastasis by Inhibiting M2-Like Polarization of Macrophages publication-title: Pharmacol Res doi: 10.1016/j.phrs.2018.05.002 – volume: 38 year: 2018 ident: B59 article-title: Myofibroblasts in Macular Fibrosis Secondary to Neovascular Age-Related Macular Degeneration - the Potential Sources and Molecular Cues for Their Recruitment and Activation publication-title: EBioMedicine doi: 10.1016/j.ebiom.2018.11.029 – volume: 16 year: 2012 ident: B24 article-title: Clusterprofiler: An R Package for Comparing Biological Themes Among Gene Clusters publication-title: OMICS: A J Integr Biol doi: 10.1089/omi.2011.0118 – volume: 10 year: 2017 ident: B54 article-title: Diverse Roles of Macrophages in Intraocular Neovascular Diseases: A Review publication-title: Int J Ophthalmol doi: 10.18240/ijo.2017.12.18 – volume: 21 start-page: 797 year: 2012 ident: B52 article-title: Matrix Metalloproteinases in Diabetic Retinopathy: Potential Role of MMP-9 publication-title: Expert Opin Investig Drugs doi: 10.1517/13543784.2012.681043 – volume: 99 year: 2015 ident: B55 article-title: Overexpression of CD163 in Vitreous and Fibrovascular Membranes of Patients With Proliferative Diabetic Retinopathy: Possible Involvement of Periostin publication-title: Br J Ophthalmol doi: 10.1136/bjophthalmol-2014-305321 – volume: 45 start-page: 3896 year: 2004 ident: B10 article-title: The Involvement of the Rho-Kinase Pathway and Its Regulation in Cytokine-Induced Collagen Gel Contraction by Hyalocytes publication-title: Invest Ophthalmol Vis Sci doi: 10.1167/iovs.03-1330 – volume: 76 year: 1992 ident: B13 article-title: Proliferative Retinal Diseases: Myofibroblasts Cause Chronic Vitreoretinal Traction publication-title: Br J Ophthalmol doi: 10.1136/bjo.76.9.550 – volume: 105 year: 2008 ident: B60 article-title: Role of TGF- in Proliferative Vitreoretinal Diseases and ROCK as a Therapeutic Target publication-title: Proc Natl Acad Sci doi: 10.1073/pnas.0804054105 |
| SSID | ssj0000493335 |
| Score | 2.4564617 |
| Snippet | Retinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease... BackgroundRetinal neovascularization (RNV) membranes can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage... |
| SourceID | doaj pubmedcentral proquest pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 757607 |
| SubjectTerms | Adult Aged Cell Transdifferentiation Cells, Cultured Computational Biology Diabetic Retinopathy - complications Diabetic Retinopathy - drug therapy Diabetic Retinopathy - metabolism Diabetic Retinopathy - pathology Drug Repositioning Endothelial Cells - metabolism Endothelial Cells - pathology Epiretinal Membrane - metabolism Epiretinal Membrane - pathology Eye Proteins - biosynthesis Eye Proteins - genetics Female Gene Ontology Humans hyalocytes Imatinib Mesylate - therapeutic use Immunologic Factors - therapeutic use Immunology Male Middle Aged myofibroblasts Myofibroblasts - pathology proliferative diabetic retinopathy (PDR) retinal neovascularization (RNV) Retinal Neovascularization - etiology Retinal Neovascularization - metabolism Retinal Neovascularization - pathology Retinal Perforations - pathology RNA sequencing Single-Cell Analysis Transcriptome transdifferentiation Vitreous Body - immunology Vitreous Body - pathology Young Adult |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3fi9QwEA5yIPginj-rp0TwSajXNmnaPurpsQp7yOnBvYUknXh7uO3hdh_6D_l3OpPsll0RffG1TWiab5KZIZnvY-wVeGGJ-C1FV-xSaWuHS0oRjasHaJySbajin5-p2YX8dFle7kh90Z2wSA8cJ-7YZ0QwDujX6kb6QlgnFECNUbeAQpWB5xN93k4ydR3jXiFEGY8xMQtrjv1iuVxjPljkbyqMsUk-dscRBb7-PwWZv9-V3HE-p_fY3U3UyN_G0R6yW9DdZ7ejjuT4gP382KXv4Wa44vOt2i0_mZiYY6El7z0_g-nmKZ_DEhNl3Oj4l_U3OmRaccPPsTvHMJbPRoNebhwgHfp0PqIFWlKeMauBB--21VUZIrJ80fHPpP_jITKJ83jTZuH4OdVU9yR8PD5kF6cfvp7M0o0AQ-pwaQ5pLR00OJMO2qLJnQSB4R9ImwknvBGqMtCW0GZOKWmkz2s6HW5LTLlMgUhb8YgddH0HTxg31oOVivYMJ9tC2hwtgah2lMlq4yFh2RYN7Tbs5CSS8V1jlkIA6gCgJgB1BDBhr6cuN5Ga42-N3xHEU0Ni1Q4P0Nb0xtb0v2wtYS-3BqJxFdLRCuLUr1cak8gGf78SRcIeR4OZPkW1uqWqsoRVe6a0N5b9N93iKjB9ExldkYun_2Pwz9gdmo9QR1kcsYPhxxqeY0A12Bdh7fwCtNQiRA priority: 102 providerName: Directory of Open Access Journals |
| Title | In-Depth Molecular Characterization of Neovascular Membranes Suggests a Role for Hyalocyte-to-Myofibroblast Transdifferentiation in Proliferative Diabetic Retinopathy |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/34795670 https://www.proquest.com/docview/2599180732 https://pubmed.ncbi.nlm.nih.gov/PMC8593213 https://doaj.org/article/f02067e509894f23bc36ee86663e2653 |
| Volume | 12 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3fb5RAEN40NSa-GH-L1mZNfDKhArss3ENjtFpPExpTveTeCLvMttf0oN5xifxD_p3OsEA8c_HJl3vg2AD7zTAz7M73MfYKrNBE_OZjKDa-1KlBl1JE42oBJkbJsuviz87UdCa_zOP5HhvkrfoJXO8s7UhPara6Pvr5o32LDn9MFSfG2zd2sVxusNSLwqME02fqLb-FgSkhQYOsz_avXDIshIjd2ubukVvRqSPx35V5_r2B8o-IdHqP3e1TSf7OYX-f7UH1gN124pLtQ_brc-V_gJvmkmeDBC4_GemZXfclry0_g3E7Ks9gidUzvv34t80FrTytecHPcTjH3JZP2wJDX9uA39R-1qJZapKjKdYN70LeILbSOLj5ouJfSRTIgqMX5277zcLwc2q0rkkNuX3EZqcfv59M_V6VwTfor42fSgMTnEkDZTQJjQSBOSFIHQgjbCFUUkAZQxkYpWQhbZjSknEZYx1WRAi_Fo_ZflVX8JTxQlvQUtGLxMgykjpE8yD-HVUEaWHBY8GARm56ynJSzrjOsXQhAPMOwJwAzB2AHns9DrlxfB3_Ovk9QTyeSFTb3YF6dZH3npvbgBjuAROrdCJtJLQRCiDFsk9ApGLhsZeDgeTomrTegjjVm3WOleUEHz8RkceeOIMZL0UNvLFKAo8lW6a0dS_b_1SLy47-mxjqolA8-x83_5zdofnomiujA7bfrDbwArOsRh92Xyfw99M8POz86DdKxC05 |
| linkProvider | Scholars Portal |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=In-Depth+Molecular+Characterization+of+Neovascular+Membranes+Suggests+a+Role+for+Hyalocyte-to-Myofibroblast+Transdifferentiation+in+Proliferative+Diabetic+Retinopathy&rft.jtitle=Frontiers+in+immunology&rft.au=Stefaniya+Konstantinova+Boneva&rft.au=Julian+Wolf&rft.au=Rozina+Ida+Hajd%C3%BA&rft.au=Rozina+Ida+Hajd%C3%BA&rft.date=2021-11-02&rft.pub=Frontiers+Media+S.A&rft.eissn=1664-3224&rft.volume=12&rft_id=info:doi/10.3389%2Ffimmu.2021.757607&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_f02067e509894f23bc36ee86663e2653 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1664-3224&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1664-3224&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1664-3224&client=summon |