Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes
Recent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce i...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2016-08, Vol.57 (10), p.4264-4271 |
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| description | Recent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce inflammatory changes in nearby cells.
Laser capture microdissection was used to isolate the outer retina (photoreceptors) from the inner retina in nondiabetic and diabetic mice. Diabetes-induced changes in the expression of inflammatory targets were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. Cell culture experiments were carried out to determine if photoreceptors in vitro and ex vivo release soluble mediators that can stimulate nearby cells. Photoreceptor contribution to leukocyte-mediated endothelial cell death was tested using coculture models.
Messenger ribonucleic acid and protein expression levels for inflammatory proteins intercellular adhesion molecule 1 (ICAM1), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) were increased in photoreceptors cells in diabetes. In vitro and ex vivo studies show that photoreceptor cells in elevated glucose release mediators that can induce tumor necrosis factor-α in leukocytes and endothelial cells, but not in glia. The soluble mediators released by photoreceptor cells in elevated glucose are regulated by transforming growth factor β-activated kinase 1 and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling. In contrast to enhanced leukocyte-mediated killing of endothelial cells by leukocytes from wild-type diabetic mice, leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill endothelial cells.
These data indicate that photoreceptor cells are a source of inflammatory proteins in diabetes, and their release of soluble mediators can contribute to the death of retinal capillaries in diabetes. |
| doi_str_mv | 10.1167/iovs.16-19859 |
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Laser capture microdissection was used to isolate the outer retina (photoreceptors) from the inner retina in nondiabetic and diabetic mice. Diabetes-induced changes in the expression of inflammatory targets were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. Cell culture experiments were carried out to determine if photoreceptors in vitro and ex vivo release soluble mediators that can stimulate nearby cells. Photoreceptor contribution to leukocyte-mediated endothelial cell death was tested using coculture models.
Messenger ribonucleic acid and protein expression levels for inflammatory proteins intercellular adhesion molecule 1 (ICAM1), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) were increased in photoreceptors cells in diabetes. In vitro and ex vivo studies show that photoreceptor cells in elevated glucose release mediators that can induce tumor necrosis factor-α in leukocytes and endothelial cells, but not in glia. The soluble mediators released by photoreceptor cells in elevated glucose are regulated by transforming growth factor β-activated kinase 1 and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling. In contrast to enhanced leukocyte-mediated killing of endothelial cells by leukocytes from wild-type diabetic mice, leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill endothelial cells.
These data indicate that photoreceptor cells are a source of inflammatory proteins in diabetes, and their release of soluble mediators can contribute to the death of retinal capillaries in diabetes.</description><identifier>ISSN: 1552-5783</identifier><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>DOI: 10.1167/iovs.16-19859</identifier><identifier>PMID: 27548900</identifier><language>eng</language><publisher>United States: The Association for Research in Vision and Ophthalmology</publisher><subject>Animals ; Cell Death - physiology ; Cells, Cultured ; Diabetes Mellitus, Experimental - genetics ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Experimental - pathology ; Diabetic Retinopathy - genetics ; Diabetic Retinopathy - metabolism ; Diabetic Retinopathy - pathology ; Inflammation Mediators - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Photoreceptor Cells - metabolism ; Photoreceptor Cells - pathology ; Real-Time Polymerase Chain Reaction ; Retina ; RNA - genetics</subject><ispartof>Investigative ophthalmology & visual science, 2016-08, Vol.57 (10), p.4264-4271</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-43f6e77c0d7c5bf4139322ba83889f7c82c62d9c0b158ac86b453c40a9235b593</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015981/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015981/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27548900$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tonade, Deoye</creatorcontrib><creatorcontrib>Liu, Haitao</creatorcontrib><creatorcontrib>Kern, Timothy S</creatorcontrib><title>Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>Recent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce inflammatory changes in nearby cells.
Laser capture microdissection was used to isolate the outer retina (photoreceptors) from the inner retina in nondiabetic and diabetic mice. Diabetes-induced changes in the expression of inflammatory targets were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. Cell culture experiments were carried out to determine if photoreceptors in vitro and ex vivo release soluble mediators that can stimulate nearby cells. Photoreceptor contribution to leukocyte-mediated endothelial cell death was tested using coculture models.
Messenger ribonucleic acid and protein expression levels for inflammatory proteins intercellular adhesion molecule 1 (ICAM1), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) were increased in photoreceptors cells in diabetes. In vitro and ex vivo studies show that photoreceptor cells in elevated glucose release mediators that can induce tumor necrosis factor-α in leukocytes and endothelial cells, but not in glia. The soluble mediators released by photoreceptor cells in elevated glucose are regulated by transforming growth factor β-activated kinase 1 and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling. In contrast to enhanced leukocyte-mediated killing of endothelial cells by leukocytes from wild-type diabetic mice, leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill endothelial cells.
These data indicate that photoreceptor cells are a source of inflammatory proteins in diabetes, and their release of soluble mediators can contribute to the death of retinal capillaries in diabetes.</description><subject>Animals</subject><subject>Cell Death - physiology</subject><subject>Cells, Cultured</subject><subject>Diabetes Mellitus, Experimental - genetics</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetic Retinopathy - genetics</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>Diabetic Retinopathy - pathology</subject><subject>Inflammation Mediators - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Photoreceptor Cells - metabolism</subject><subject>Photoreceptor Cells - pathology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Retina</subject><subject>RNA - genetics</subject><issn>1552-5783</issn><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctLxDAQxoMovo9eJUcv1TyaNrkIsj5hRQ96Dmk6tZG2WZtU8L83u-qyzmUG5sc3jw-hE0rOKS3KC-c_wzktMqqkUFtonwrBMlFKvr1R76GDEN4JYZQysov2WClyqQjZR-1z66MfwcIiJTyDrgv4efT1ZAE_DE1n-t6kzhd-hNotq4BfWhPxzA9xdNUUAUePb4baxxY6Z7qVBr4GE1vsBnztTAURwhHaaUwX4Pg3H6LX25uX2X02f7p7mF3NM8tlGbOcNwWUpSV1aUXV5JQrzlhlJJdSNaWVzBasVpZUVEhjZVHlgtucGMW4qITih-jyR3cxVT3UFtKaptOL0fVm_NLeOP2_M7hWv_lPLQgVStIkcPYrMPqPCULUvQs23WQG8FPQNDHpdSkSmv2gdvQhjNCsx1Cil-7opTuaFnrlTuJPN3db03928G9Dj42B</recordid><startdate>20160801</startdate><enddate>20160801</enddate><creator>Tonade, Deoye</creator><creator>Liu, Haitao</creator><creator>Kern, Timothy S</creator><general>The Association for Research in Vision and Ophthalmology</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160801</creationdate><title>Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes</title><author>Tonade, Deoye ; Liu, Haitao ; Kern, Timothy S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-43f6e77c0d7c5bf4139322ba83889f7c82c62d9c0b158ac86b453c40a9235b593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Cell Death - physiology</topic><topic>Cells, Cultured</topic><topic>Diabetes Mellitus, Experimental - genetics</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Diabetic Retinopathy - genetics</topic><topic>Diabetic Retinopathy - metabolism</topic><topic>Diabetic Retinopathy - pathology</topic><topic>Inflammation Mediators - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Photoreceptor Cells - metabolism</topic><topic>Photoreceptor Cells - pathology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Retina</topic><topic>RNA - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tonade, Deoye</creatorcontrib><creatorcontrib>Liu, Haitao</creatorcontrib><creatorcontrib>Kern, Timothy S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tonade, Deoye</au><au>Liu, Haitao</au><au>Kern, Timothy S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2016-08-01</date><risdate>2016</risdate><volume>57</volume><issue>10</issue><spage>4264</spage><epage>4271</epage><pages>4264-4271</pages><issn>1552-5783</issn><issn>0146-0404</issn><eissn>1552-5783</eissn><abstract>Recent studies suggest that photoreceptor cells regulate local inflammation in the retina in diabetes. The purpose of this study was to determine if photoreceptor cells themselves produce inflammatory proteins in diabetes and if soluble factors released by photoreceptors in elevated glucose induce inflammatory changes in nearby cells.
Laser capture microdissection was used to isolate the outer retina (photoreceptors) from the inner retina in nondiabetic and diabetic mice. Diabetes-induced changes in the expression of inflammatory targets were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. Cell culture experiments were carried out to determine if photoreceptors in vitro and ex vivo release soluble mediators that can stimulate nearby cells. Photoreceptor contribution to leukocyte-mediated endothelial cell death was tested using coculture models.
Messenger ribonucleic acid and protein expression levels for inflammatory proteins intercellular adhesion molecule 1 (ICAM1), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2) were increased in photoreceptors cells in diabetes. In vitro and ex vivo studies show that photoreceptor cells in elevated glucose release mediators that can induce tumor necrosis factor-α in leukocytes and endothelial cells, but not in glia. The soluble mediators released by photoreceptor cells in elevated glucose are regulated by transforming growth factor β-activated kinase 1 and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling. In contrast to enhanced leukocyte-mediated killing of endothelial cells by leukocytes from wild-type diabetic mice, leukocytes from diabetic mice lacking photoreceptor cells (opsin-/-) did not kill endothelial cells.
These data indicate that photoreceptor cells are a source of inflammatory proteins in diabetes, and their release of soluble mediators can contribute to the death of retinal capillaries in diabetes.</abstract><cop>United States</cop><pub>The Association for Research in Vision and Ophthalmology</pub><pmid>27548900</pmid><doi>10.1167/iovs.16-19859</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Cell Death - physiology Cells, Cultured Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Diabetic Retinopathy - genetics Diabetic Retinopathy - metabolism Diabetic Retinopathy - pathology Inflammation Mediators - metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Photoreceptor Cells - metabolism Photoreceptor Cells - pathology Real-Time Polymerase Chain Reaction Retina RNA - genetics |
| title | Photoreceptor Cells Produce Inflammatory Mediators That Contribute to Endothelial Cell Death in Diabetes |
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