Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation
Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment. 12 patient...
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| Veröffentlicht in: | PloS one 2019-06, Vol.14 (6), p.e0217548-e0217548 |
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| creator | Josifovska, Natasha Lumi, Xhevat Szatmari-Tóth, Mária Kristóf, Endre Russell, Greg Nagymihály, Richárd Anisimova, Natalia Malyugin, Boris Kolko, Miriam Ivastinović, Domagoj Petrovski, Goran |
| description | Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment.
12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).
OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.
Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina. |
| doi_str_mv | 10.1371/journal.pone.0217548 |
| format | Article |
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12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).
OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.
Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0217548</identifier><identifier>PMID: 31185026</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Antigens, Differentiation - immunology ; Apoptosis ; Apoptosis - immunology ; Biochemistry ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Care and treatment ; CD34 antigen ; Cell division ; Conglomerates ; Criminal investigation ; Cytokines ; Diagnosis ; Diagnostic systems ; Epithelial Cells - immunology ; Epithelial Cells - pathology ; Eye Proteins - immunology ; Female ; Flow cytometry ; Genomics ; Glial fibrillary acidic protein ; Health aspects ; Hospitals ; Humans ; Immune response ; Immune system ; Immunohistochemistry ; Inflammation ; Inflammation - immunology ; Inflammation - pathology ; Inflammation - surgery ; Macrophages ; Macrophages - immunology ; Macrophages - pathology ; Male ; Medical research ; Medicine and Health Sciences ; Microglia ; Microglia - immunology ; Microglia - pathology ; Microglial cells ; Microsurgery ; Middle Aged ; Molecular biology ; Nestin ; NF-κB protein ; Oct-4 protein ; Patients ; Phagocytes ; Phagocytosis ; Pluripotency ; Prognosis ; Protein arrays ; Retina ; Retinal detachment ; Retinal Detachment - immunology ; Retinal Detachment - pathology ; Retinal Detachment - surgery ; Retinal Pigment Epithelium - immunology ; Retinal Pigment Epithelium - pathology ; Retinal Pigment Epithelium - surgery ; Stem cells ; Stem Cells - immunology ; Stem Cells - pathology ; Surgery</subject><ispartof>PloS one, 2019-06, Vol.14 (6), p.e0217548-e0217548</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Josifovska 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>2019 Josifovska et al 2019 Josifovska et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c716t-74306a16f73ffbb1c373148039db5f3b8048e777d96fe7ba3793c458f2d0fcab3</citedby><cites>FETCH-LOGICAL-c716t-74306a16f73ffbb1c373148039db5f3b8048e777d96fe7ba3793c458f2d0fcab3</cites><orcidid>0000-0002-6105-1632</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559703/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559703/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,26544,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31185026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Josifovska, Natasha</creatorcontrib><creatorcontrib>Lumi, Xhevat</creatorcontrib><creatorcontrib>Szatmari-Tóth, Mária</creatorcontrib><creatorcontrib>Kristóf, Endre</creatorcontrib><creatorcontrib>Russell, Greg</creatorcontrib><creatorcontrib>Nagymihály, Richárd</creatorcontrib><creatorcontrib>Anisimova, Natalia</creatorcontrib><creatorcontrib>Malyugin, Boris</creatorcontrib><creatorcontrib>Kolko, Miriam</creatorcontrib><creatorcontrib>Ivastinović, Domagoj</creatorcontrib><creatorcontrib>Petrovski, Goran</creatorcontrib><title>Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment.
12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).
OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.
Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.</description><subject>Adult</subject><subject>Aged</subject><subject>Antigens, Differentiation - immunology</subject><subject>Apoptosis</subject><subject>Apoptosis - immunology</subject><subject>Biochemistry</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Care and treatment</subject><subject>CD34 antigen</subject><subject>Cell division</subject><subject>Conglomerates</subject><subject>Criminal investigation</subject><subject>Cytokines</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Epithelial Cells - immunology</subject><subject>Epithelial Cells - pathology</subject><subject>Eye Proteins - immunology</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Genomics</subject><subject>Glial fibrillary acidic protein</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Inflammation - 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surgery</subject><subject>Retinal Pigment Epithelium - immunology</subject><subject>Retinal Pigment Epithelium - pathology</subject><subject>Retinal Pigment Epithelium - surgery</subject><subject>Stem cells</subject><subject>Stem Cells - immunology</subject><subject>Stem Cells - pathology</subject><subject>Surgery</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>3HK</sourceid><sourceid>DOA</sourceid><recordid>eNqNk01v1DAQhiMEoqXwDxBEQkJw2MWO49i5IFUrCitVqsTX1XL8sevi2Fvbqei_x2mzZYN6QDkkcp55x_POTFG8hGAJEYEfLv0QHLfLnXdqCSpIcE0fFcewRdWiqQB6fPB9VDyL8RIAjGjTPC2OEIQUg6o5LvzKGmcEtyV3suy9VWKwPJQ9D79UiKVxZVDJ5ESlVImLba9cWpwF35fbm50KQekcksy1KnfeuBTL5MuYVF8KZW28VTVOW973PBnvnhdPNLdRvZjeJ8WPs0_fV18W5xef16vT84UgsEkLUiPQcNhogrTuOigQQbCmALWywxp1FNRUEUJk22hFOo5Ii0SNqa4k0IJ36KR4fae7sz6yyavIqio7ALIjNBPrO0J6fsl2weSSb5jnht0e-LBhPCQjrGIdQVhxKJHumrqTLZcQSKyyDpSyRXXW-jhlG7peSZE9CtzOROd_nNmyjb9mDcYtAejvdUUwMdvNnA-cQUBxxQhGoMrEuylF8FeDion1Jo4ec6f8MFZWVxS1sIUZffMP-nD9E7XhucTcI59vJkZRdoopxZTUeNRaPkDlR6reiDx62uTzWcD7WUBmkvqdNnyIka2_ff1_9uLnnH17wG4Vt2kbvR3GoYpzsN5b6WPM83nfBgjYuDl7N9i4OWzanBz26rCF90H7VUF_ANHZE3c</recordid><startdate>20190611</startdate><enddate>20190611</enddate><creator>Josifovska, Natasha</creator><creator>Lumi, Xhevat</creator><creator>Szatmari-Tóth, Mária</creator><creator>Kristóf, Endre</creator><creator>Russell, Greg</creator><creator>Nagymihály, Richárd</creator><creator>Anisimova, Natalia</creator><creator>Malyugin, Boris</creator><creator>Kolko, Miriam</creator><creator>Ivastinović, Domagoj</creator><creator>Petrovski, Goran</creator><general>Public Library of Science</general><general>PLOS</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>3HK</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6105-1632</orcidid></search><sort><creationdate>20190611</creationdate><title>Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation</title><author>Josifovska, Natasha ; Lumi, Xhevat ; Szatmari-Tóth, Mária ; Kristóf, Endre ; Russell, Greg ; Nagymihály, Richárd ; Anisimova, Natalia ; Malyugin, Boris ; Kolko, Miriam ; Ivastinović, Domagoj ; Petrovski, Goran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c716t-74306a16f73ffbb1c373148039db5f3b8048e777d96fe7ba3793c458f2d0fcab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antigens, Differentiation - 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immunology</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Microglia</topic><topic>Microglia - immunology</topic><topic>Microglia - pathology</topic><topic>Microglial cells</topic><topic>Microsurgery</topic><topic>Middle Aged</topic><topic>Molecular biology</topic><topic>Nestin</topic><topic>NF-κB protein</topic><topic>Oct-4 protein</topic><topic>Patients</topic><topic>Phagocytes</topic><topic>Phagocytosis</topic><topic>Pluripotency</topic><topic>Prognosis</topic><topic>Protein arrays</topic><topic>Retina</topic><topic>Retinal detachment</topic><topic>Retinal Detachment - immunology</topic><topic>Retinal Detachment - pathology</topic><topic>Retinal Detachment - surgery</topic><topic>Retinal Pigment Epithelium - immunology</topic><topic>Retinal Pigment Epithelium - pathology</topic><topic>Retinal Pigment Epithelium - surgery</topic><topic>Stem cells</topic><topic>Stem Cells - immunology</topic><topic>Stem Cells - pathology</topic><topic>Surgery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Josifovska, Natasha</creatorcontrib><creatorcontrib>Lumi, Xhevat</creatorcontrib><creatorcontrib>Szatmari-Tóth, Mária</creatorcontrib><creatorcontrib>Kristóf, Endre</creatorcontrib><creatorcontrib>Russell, Greg</creatorcontrib><creatorcontrib>Nagymihály, Richárd</creatorcontrib><creatorcontrib>Anisimova, Natalia</creatorcontrib><creatorcontrib>Malyugin, Boris</creatorcontrib><creatorcontrib>Kolko, Miriam</creatorcontrib><creatorcontrib>Ivastinović, Domagoj</creatorcontrib><creatorcontrib>Petrovski, Goran</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Josifovska, Natasha</au><au>Lumi, Xhevat</au><au>Szatmari-Tóth, Mária</au><au>Kristóf, Endre</au><au>Russell, Greg</au><au>Nagymihály, Richárd</au><au>Anisimova, Natalia</au><au>Malyugin, Boris</au><au>Kolko, Miriam</au><au>Ivastinović, Domagoj</au><au>Petrovski, Goran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-06-11</date><risdate>2019</risdate><volume>14</volume><issue>6</issue><spage>e0217548</spage><epage>e0217548</epage><pages>e0217548-e0217548</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Retinal detachment (RD) is one of the most frequently diagnosed ophthalmologic conditions requiring prompt surgical intervention. Combination of proper surgical technique and new diagnostic markers, both clinical and molecular, can help improve the diagnosis and prognosis of RD treatment.
12 patients with rhegmatogenous RD (rRD) were included into the study after obtaining patient consent and Regional Ethical Approval (average age: 58.1 ± 17.4 years). OCT was performed before and after 23G vitrectomy for RD. Pure subretinal fluid (SRF) was collected during surgery and analyzed by protein array profiling on a panel of 105 inflammatory cytokines (Human XL Cytokine Array), while the effect of SRF upon human macrophages-driven phagocytosis of apoptotic retinal pigment epithelial (RPE) cells ex vivo was quantified by flow cytometry. Immunohistochemistry (IHC) of retinectomized tissue due to PVR caused by RD was performed to determine presence of markers for microglial cells (CD34), macrophages and activated microglia (CD68), regulator of the immune response to infection (NFkB), progenitor and stem cell marker (Sox2), pluripotency marker (Oct4) and intermediate filament markers (GFAP and Nestin).
OCT of fresh RD patients contained pre-operatively hyper reflective points (HRPs) at the detached neuroretina border and proximal to the RPE layer-their size and number decreased following successful reattachment surgery. IHC of the retinectomized tissue from detached retina due to severe PVR showed presence of cell conglomerates at the detached neuroretina border which were positive for CD68, NFkB, Sox2 and GFAP, less positive for CD47 and Nestin and negative for Oct4 and CD34. The SRF contained at least 37 cytokines with higher, and 4 cytokine with lower concentration compared to that in vitreous from non-RD pathology; when used as conditional medium to human macrophages ex vivo, the SRF doubled their capacity for engulfing dying RPEs.
Fresh RD can be hallmarked by presence of HRPs at the detached neuroretina border on OCT; the HRPs decrease in size and number after successful reattachment surgery, and likely resemble the macrophage conglomerates seen by IHC. The neuroretina in RD contains progenitor/stem-like cells and signs of inflammatory reaction, while the SRF contains inflammatory cytokines and other factors which increase the ability of professional phagocytes to engulf dying RPE, or for that matter, other dying cells in the retina.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31185026</pmid><doi>10.1371/journal.pone.0217548</doi><tpages>e0217548</tpages><orcidid>https://orcid.org/0000-0002-6105-1632</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-06, Vol.14 (6), p.e0217548-e0217548 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2238602038 |
| source | MEDLINE; NORA - Norwegian Open Research Archives; 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 | Adult Aged Antigens, Differentiation - immunology Apoptosis Apoptosis - immunology Biochemistry Biological markers Biology and Life Sciences Biomarkers Care and treatment CD34 antigen Cell division Conglomerates Criminal investigation Cytokines Diagnosis Diagnostic systems Epithelial Cells - immunology Epithelial Cells - pathology Eye Proteins - immunology Female Flow cytometry Genomics Glial fibrillary acidic protein Health aspects Hospitals Humans Immune response Immune system Immunohistochemistry Inflammation Inflammation - immunology Inflammation - pathology Inflammation - surgery Macrophages Macrophages - immunology Macrophages - pathology Male Medical research Medicine and Health Sciences Microglia Microglia - immunology Microglia - pathology Microglial cells Microsurgery Middle Aged Molecular biology Nestin NF-κB protein Oct-4 protein Patients Phagocytes Phagocytosis Pluripotency Prognosis Protein arrays Retina Retinal detachment Retinal Detachment - immunology Retinal Detachment - pathology Retinal Detachment - surgery Retinal Pigment Epithelium - immunology Retinal Pigment Epithelium - pathology Retinal Pigment Epithelium - surgery Stem cells Stem Cells - immunology Stem Cells - pathology Surgery |
| title | Clinical and molecular markers in retinal detachment-From hyperreflective points to stem cells and inflammation |
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