Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm
ABSTRACT The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of th...
Gespeichert in:
| Veröffentlicht in: | The FASEB journal 2014-05, Vol.28 (5), p.2038-2046 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2046 |
|---|---|
| container_issue | 5 |
| container_start_page | 2038 |
| container_title | The FASEB journal |
| container_volume | 28 |
| creator | Noda, Kousuke Nakao, Shintaro Zandi, Souska Sun, Dawei Hayes, K. C. Hafezi‐Moghadam, Ali |
| description | ABSTRACT
The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)‐injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM‐1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM‐1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM‐1) expression, however, was unaffected by the disease state. As opposed to the STZ‐induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM‐1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 μIU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ‐induced T1D.—Noda, K., Nakao, S., Zandi, S., Sun, D., Hayes, K. C., Hafezi‐Moghadam, A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 28, 2038–2046 (2014). www.fasebj.org |
| doi_str_mv | 10.1096/fj.12-215715 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3986844</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1521332622</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4995-d8d2d1847501457ca1dceeeb2e75e99b6d26197172b32690d7c5d837a61f81303</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi1ERbeFG2fkIwfSepzEsTkglYqFokpIfJwtJ57sepXYIfa2yr_H1S4VvXAZa-RnnhnpJeQ1sAtgSlz2uwvgBYe6gfoZWUFdskJIwZ6TFZOKF0KU8pScxbhjjAED8YKc8irTivMVmb5jcj5MJm0X6jw11Ic7HOgYbK6hpyMm04bBdTQu3s5hRGq8pWmZkHJqnWkxYXxPPd7n-eg220SDp2mLue0HM44mhXmhk5mNdZvxJTnpzRDx1fE9J7_Wn35efyluv32-ub66LbpKqbqw0nILsmpqBvnYzoDtELHl2NSoVCssF6AaaHhbcqGYbbrayrIxAnoJJSvPyYeDd9q3I-Zhn2Yz6Gl2o5kXHYzTT3-82-pNuNOlkkJWVRa8PQrm8HuPMenRxQ6HwXgM-6ih5lDm3Zxn9N0B7eYQ44z94xpg-iEk3e80cH0IKeNv_j3tEf6bSgbkAbh3Ay7_len1j498_RX40f0Hj4ufIw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1521332622</pqid></control><display><type>article</type><title>Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Alma/SFX Local Collection</source><creator>Noda, Kousuke ; Nakao, Shintaro ; Zandi, Souska ; Sun, Dawei ; Hayes, K. C. ; Hafezi‐Moghadam, Ali</creator><creatorcontrib>Noda, Kousuke ; Nakao, Shintaro ; Zandi, Souska ; Sun, Dawei ; Hayes, K. C. ; Hafezi‐Moghadam, Ali</creatorcontrib><description>ABSTRACT
The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)‐injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM‐1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM‐1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM‐1) expression, however, was unaffected by the disease state. As opposed to the STZ‐induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM‐1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 μIU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ‐induced T1D.—Noda, K., Nakao, S., Zandi, S., Sun, D., Hayes, K. C., Hafezi‐Moghadam, A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 28, 2038–2046 (2014). www.fasebj.org</description><identifier>ISSN: 0892-6638</identifier><identifier>EISSN: 1530-6860</identifier><identifier>DOI: 10.1096/fj.12-215715</identifier><identifier>PMID: 24571922</identifier><language>eng</language><publisher>United States: Federation of American Societies for Experimental Biology</publisher><subject>adhesion molecules ; adipokines ; Adiponectin - metabolism ; Animals ; Blood-Retinal Barrier - metabolism ; Cell Adhesion ; Diabetes Complications - pathology ; Diabetes Mellitus, Type 2 - pathology ; Diabetic Retinopathy - pathology ; Disease Models, Animal ; Female ; Glycated Hemoglobin A - metabolism ; Inflammation - pathology ; Insulin - blood ; Intercellular Adhesion Molecule-1 - metabolism ; Leptin - blood ; Leukocytes - cytology ; Lipids - blood ; Male ; Metabolic Syndrome - complications ; Nile grass rat ; Rats ; Research Communications ; Retina - metabolism ; Retinal Vessels - metabolism ; Streptozocin ; Triglycerides - metabolism ; Vascular Cell Adhesion Molecule-1 - metabolism</subject><ispartof>The FASEB journal, 2014-05, Vol.28 (5), p.2038-2046</ispartof><rights>FASEB</rights><rights>FASEB 2014 FASEB</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4995-d8d2d1847501457ca1dceeeb2e75e99b6d26197172b32690d7c5d837a61f81303</citedby><cites>FETCH-LOGICAL-c4995-d8d2d1847501457ca1dceeeb2e75e99b6d26197172b32690d7c5d837a61f81303</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1096%2Ffj.12-215715$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1096%2Ffj.12-215715$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24571922$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noda, Kousuke</creatorcontrib><creatorcontrib>Nakao, Shintaro</creatorcontrib><creatorcontrib>Zandi, Souska</creatorcontrib><creatorcontrib>Sun, Dawei</creatorcontrib><creatorcontrib>Hayes, K. C.</creatorcontrib><creatorcontrib>Hafezi‐Moghadam, Ali</creatorcontrib><title>Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm</title><title>The FASEB journal</title><addtitle>FASEB J</addtitle><description>ABSTRACT
The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)‐injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM‐1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM‐1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM‐1) expression, however, was unaffected by the disease state. As opposed to the STZ‐induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM‐1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 μIU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ‐induced T1D.—Noda, K., Nakao, S., Zandi, S., Sun, D., Hayes, K. C., Hafezi‐Moghadam, A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 28, 2038–2046 (2014). www.fasebj.org</description><subject>adhesion molecules</subject><subject>adipokines</subject><subject>Adiponectin - metabolism</subject><subject>Animals</subject><subject>Blood-Retinal Barrier - metabolism</subject><subject>Cell Adhesion</subject><subject>Diabetes Complications - pathology</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diabetic Retinopathy - pathology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Glycated Hemoglobin A - metabolism</subject><subject>Inflammation - pathology</subject><subject>Insulin - blood</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Leptin - blood</subject><subject>Leukocytes - cytology</subject><subject>Lipids - blood</subject><subject>Male</subject><subject>Metabolic Syndrome - complications</subject><subject>Nile grass rat</subject><subject>Rats</subject><subject>Research Communications</subject><subject>Retina - metabolism</subject><subject>Retinal Vessels - metabolism</subject><subject>Streptozocin</subject><subject>Triglycerides - metabolism</subject><subject>Vascular Cell Adhesion Molecule-1 - metabolism</subject><issn>0892-6638</issn><issn>1530-6860</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi1ERbeFG2fkIwfSepzEsTkglYqFokpIfJwtJ57sepXYIfa2yr_H1S4VvXAZa-RnnhnpJeQ1sAtgSlz2uwvgBYe6gfoZWUFdskJIwZ6TFZOKF0KU8pScxbhjjAED8YKc8irTivMVmb5jcj5MJm0X6jw11Ic7HOgYbK6hpyMm04bBdTQu3s5hRGq8pWmZkHJqnWkxYXxPPd7n-eg220SDp2mLue0HM44mhXmhk5mNdZvxJTnpzRDx1fE9J7_Wn35efyluv32-ub66LbpKqbqw0nILsmpqBvnYzoDtELHl2NSoVCssF6AaaHhbcqGYbbrayrIxAnoJJSvPyYeDd9q3I-Zhn2Yz6Gl2o5kXHYzTT3-82-pNuNOlkkJWVRa8PQrm8HuPMenRxQ6HwXgM-6ih5lDm3Zxn9N0B7eYQ44z94xpg-iEk3e80cH0IKeNv_j3tEf6bSgbkAbh3Ay7_len1j498_RX40f0Hj4ufIw</recordid><startdate>201405</startdate><enddate>201405</enddate><creator>Noda, Kousuke</creator><creator>Nakao, Shintaro</creator><creator>Zandi, Souska</creator><creator>Sun, Dawei</creator><creator>Hayes, K. C.</creator><creator>Hafezi‐Moghadam, Ali</creator><general>Federation of American Societies for Experimental Biology</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>201405</creationdate><title>Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm</title><author>Noda, Kousuke ; Nakao, Shintaro ; Zandi, Souska ; Sun, Dawei ; Hayes, K. C. ; Hafezi‐Moghadam, Ali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4995-d8d2d1847501457ca1dceeeb2e75e99b6d26197172b32690d7c5d837a61f81303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>adhesion molecules</topic><topic>adipokines</topic><topic>Adiponectin - metabolism</topic><topic>Animals</topic><topic>Blood-Retinal Barrier - metabolism</topic><topic>Cell Adhesion</topic><topic>Diabetes Complications - pathology</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diabetic Retinopathy - pathology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Glycated Hemoglobin A - metabolism</topic><topic>Inflammation - pathology</topic><topic>Insulin - blood</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Leptin - blood</topic><topic>Leukocytes - cytology</topic><topic>Lipids - blood</topic><topic>Male</topic><topic>Metabolic Syndrome - complications</topic><topic>Nile grass rat</topic><topic>Rats</topic><topic>Research Communications</topic><topic>Retina - metabolism</topic><topic>Retinal Vessels - metabolism</topic><topic>Streptozocin</topic><topic>Triglycerides - metabolism</topic><topic>Vascular Cell Adhesion Molecule-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noda, Kousuke</creatorcontrib><creatorcontrib>Nakao, Shintaro</creatorcontrib><creatorcontrib>Zandi, Souska</creatorcontrib><creatorcontrib>Sun, Dawei</creatorcontrib><creatorcontrib>Hayes, K. C.</creatorcontrib><creatorcontrib>Hafezi‐Moghadam, Ali</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>The FASEB journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noda, Kousuke</au><au>Nakao, Shintaro</au><au>Zandi, Souska</au><au>Sun, Dawei</au><au>Hayes, K. C.</au><au>Hafezi‐Moghadam, Ali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm</atitle><jtitle>The FASEB journal</jtitle><addtitle>FASEB J</addtitle><date>2014-05</date><risdate>2014</risdate><volume>28</volume><issue>5</issue><spage>2038</spage><epage>2046</epage><pages>2038-2046</pages><issn>0892-6638</issn><eissn>1530-6860</eissn><abstract>ABSTRACT
The pathogenesis of diabetic retinopathy (DR) in metabolic syndrome (MetS) and type 2 diabetes (T2D) is not well studied, partly because an appropriate model has not been developed. Recently, we introduced a novel model of spontaneous T2D and MetS that replicates the relevant features of the human disease. In the current study, we investigated the retinal vascular changes in these animals. Experimental DR in streptozotocin (STZ)‐injected rodents is described as an inflammatory disease, in which intercellular adhesion molecule 1 (ICAM‐1) plays a key role. In comparison, advanced diabetes (HbA1c>10%) in the Nile grass rat (NGR) was associated with lower ICAM‐1 protein expression when compared with that in normal or moderately diabetic animals. Vascular cell adhesion molecule 1 (VCAM‐1) expression, however, was unaffected by the disease state. As opposed to the STZ‐induced model of DR, in diabetic NGRs, most leukocytes accumulated in the retinal arteries. Consistent with the ICAM‐1 reduction, leukocyte accumulation was significantly reduced in advanced disease. Similarly, leukocyte adhesions were significantly lower, with elevated plasma triglycerides (>200 mg/dl), and cholesterol (>240 mg/dl). However, these adhesions were significantly higher in animals with higher plasma insulin (>5 μIU/ml) and leptin (>20 ng/ml), suggesting a role for these hormones in diabetic retinal leukostasis. Diabetic NGRs showed substantial retinal endothelial injury, primarily in the microvessels, including vascular tortuosity, obliterated acellular capillaries, and pericyte ghosts. The NGR provides a convenient and realistic model for investigation of retinal changes in MetS/T2D with convincing advantages over the commonly used STZ‐induced T1D.—Noda, K., Nakao, S., Zandi, S., Sun, D., Hayes, K. C., Hafezi‐Moghadam, A. Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm. FASEB J. 28, 2038–2046 (2014). www.fasebj.org</abstract><cop>United States</cop><pub>Federation of American Societies for Experimental Biology</pub><pmid>24571922</pmid><doi>10.1096/fj.12-215715</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0892-6638 |
| ispartof | The FASEB journal, 2014-05, Vol.28 (5), p.2038-2046 |
| issn | 0892-6638 1530-6860 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3986844 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | adhesion molecules adipokines Adiponectin - metabolism Animals Blood-Retinal Barrier - metabolism Cell Adhesion Diabetes Complications - pathology Diabetes Mellitus, Type 2 - pathology Diabetic Retinopathy - pathology Disease Models, Animal Female Glycated Hemoglobin A - metabolism Inflammation - pathology Insulin - blood Intercellular Adhesion Molecule-1 - metabolism Leptin - blood Leukocytes - cytology Lipids - blood Male Metabolic Syndrome - complications Nile grass rat Rats Research Communications Retina - metabolism Retinal Vessels - metabolism Streptozocin Triglycerides - metabolism Vascular Cell Adhesion Molecule-1 - metabolism |
| title | Retinopathy in a novel model of metabolic syndrome and type 2 diabetes: new insight on the inflammatory paradigm |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T02%3A53%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Retinopathy%20in%20a%20novel%20model%20of%20metabolic%20syndrome%20and%20type%202%20diabetes:%20new%20insight%20on%20the%20inflammatory%20paradigm&rft.jtitle=The%20FASEB%20journal&rft.au=Noda,%20Kousuke&rft.date=2014-05&rft.volume=28&rft.issue=5&rft.spage=2038&rft.epage=2046&rft.pages=2038-2046&rft.issn=0892-6638&rft.eissn=1530-6860&rft_id=info:doi/10.1096/fj.12-215715&rft_dat=%3Cproquest_pubme%3E1521332622%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1521332622&rft_id=info:pmid/24571922&rfr_iscdi=true |