Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy
Abstract Purpose We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. Methods Ocular fluid and small specimens of iris and neovascular membrane were o...
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| Veröffentlicht in: | Diabetes research and clinical practice 2008-03, Vol.79 (3), p.438-445 |
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| creator | Kakehashi, Akihiro Inoda, Shigeru Mameuda, Chiho Kuroki, Masatoshi Jono, Tadashi Nagai, Ryuji Horiuchi, Seikoh Kawakami, Masanobu Kanazawa, Yasunori |
| description | Abstract Purpose We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. Methods Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. Results The mean VEGF and AGE levels in the vitreous (695.7 pg/ml and 2.4 mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9 pg/ml, p = 0.0007 and 1.3 mg/ml, p = 0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly ( r = 0.6; p = 0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. Conclusions By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina. |
| doi_str_mv | 10.1016/j.diabres.2007.10.018 |
| format | Article |
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Methods Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. Results The mean VEGF and AGE levels in the vitreous (695.7 pg/ml and 2.4 mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9 pg/ml, p = 0.0007 and 1.3 mg/ml, p = 0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly ( r = 0.6; p = 0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. Conclusions By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.</description><identifier>ISSN: 0168-8227</identifier><identifier>EISSN: 1872-8227</identifier><identifier>DOI: 10.1016/j.diabres.2007.10.018</identifier><identifier>PMID: 18053608</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Adult ; AGE ; Aged ; Aged, 80 and over ; Diabetes ; Diabetic retinopathy ; Diabetic Retinopathy - metabolism ; Diabetic Retinopathy - pathology ; Endocrinology & Metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Glycation End Products, Advanced - metabolism ; Humans ; Immunohistochemistry ; Macrophage ; Macrophages - pathology ; Male ; Middle Aged ; Receptors, Vascular Endothelial Growth Factor - metabolism ; Vascular Endothelial Growth Factor A - metabolism ; VEGF ; VEGF receptor</subject><ispartof>Diabetes research and clinical practice, 2008-03, Vol.79 (3), p.438-445</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2007 Elsevier Ireland Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-553649a6488cef4298465d87df2c75d4e4b17724853cf84cbbe0e75552de08e13</citedby><cites>FETCH-LOGICAL-c418t-553649a6488cef4298465d87df2c75d4e4b17724853cf84cbbe0e75552de08e13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.diabres.2007.10.018$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18053608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kakehashi, Akihiro</creatorcontrib><creatorcontrib>Inoda, Shigeru</creatorcontrib><creatorcontrib>Mameuda, Chiho</creatorcontrib><creatorcontrib>Kuroki, Masatoshi</creatorcontrib><creatorcontrib>Jono, Tadashi</creatorcontrib><creatorcontrib>Nagai, Ryuji</creatorcontrib><creatorcontrib>Horiuchi, Seikoh</creatorcontrib><creatorcontrib>Kawakami, Masanobu</creatorcontrib><creatorcontrib>Kanazawa, Yasunori</creatorcontrib><title>Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy</title><title>Diabetes research and clinical practice</title><addtitle>Diabetes Res Clin Pract</addtitle><description>Abstract Purpose We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. Methods Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. Results The mean VEGF and AGE levels in the vitreous (695.7 pg/ml and 2.4 mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9 pg/ml, p = 0.0007 and 1.3 mg/ml, p = 0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly ( r = 0.6; p = 0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. Conclusions By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.</description><subject>Adult</subject><subject>AGE</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Diabetes</subject><subject>Diabetic retinopathy</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>Diabetic Retinopathy - pathology</subject><subject>Endocrinology & Metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Glycation End Products, Advanced - metabolism</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Macrophage</subject><subject>Macrophages - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Receptors, Vascular Endothelial Growth Factor - metabolism</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>VEGF</subject><subject>VEGF receptor</subject><issn>0168-8227</issn><issn>1872-8227</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EoqHwE0A-cUrC2Guv3QuoqtKAVAmJr6vltWcbh13vYm8q5d_X20RC4sLFY43emXnnGULeMlgzYPWH_doH2yTMaw6gSm4NTD8jC6YVX2nO1XOyKDr99L8gr3LeA0BdCfmSXDANsqpBL4j7hp2dwhDzLozU9kO8p78229vl00sTOhynIS3p9XaTl9RGT3vr0jDu7D1mGiId09CFFlPp8oB0NoVTcKVyCnEY7bQ7viYvWttlfHOOl-Tn7ebHzefV3dftl5vru5UTTE8rWSyJK1sLrR22gl9pUUuvlW-5U9ILFA1TigstK9dq4ZoGAZWUknsEjay6JO9PfYulPwfMk-lDdth1NuJwyEZBxWtZzUJ5EpZFck7YmjGF3qajYWBmumZvznTNTHdOF7ql7t15wKHp0f-tOuMsgk8nAZY1HwImk13A6NCHQnIyfgj_HfHxnw6uCzE42_3GI-b9cEixMDTMZG7AfJ9PPF8YFIDkmlWPjvSiCQ</recordid><startdate>20080301</startdate><enddate>20080301</enddate><creator>Kakehashi, Akihiro</creator><creator>Inoda, Shigeru</creator><creator>Mameuda, Chiho</creator><creator>Kuroki, Masatoshi</creator><creator>Jono, Tadashi</creator><creator>Nagai, Ryuji</creator><creator>Horiuchi, Seikoh</creator><creator>Kawakami, Masanobu</creator><creator>Kanazawa, Yasunori</creator><general>Elsevier Ireland Ltd</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></search><sort><creationdate>20080301</creationdate><title>Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy</title><author>Kakehashi, Akihiro ; Inoda, Shigeru ; Mameuda, Chiho ; Kuroki, Masatoshi ; Jono, Tadashi ; Nagai, Ryuji ; Horiuchi, Seikoh ; Kawakami, Masanobu ; Kanazawa, Yasunori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-553649a6488cef4298465d87df2c75d4e4b17724853cf84cbbe0e75552de08e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>AGE</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Diabetes</topic><topic>Diabetic retinopathy</topic><topic>Diabetic Retinopathy - metabolism</topic><topic>Diabetic Retinopathy - pathology</topic><topic>Endocrinology & Metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Glycation End Products, Advanced - metabolism</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Macrophage</topic><topic>Macrophages - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Receptors, Vascular Endothelial Growth Factor - metabolism</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>VEGF</topic><topic>VEGF receptor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kakehashi, Akihiro</creatorcontrib><creatorcontrib>Inoda, Shigeru</creatorcontrib><creatorcontrib>Mameuda, Chiho</creatorcontrib><creatorcontrib>Kuroki, Masatoshi</creatorcontrib><creatorcontrib>Jono, Tadashi</creatorcontrib><creatorcontrib>Nagai, Ryuji</creatorcontrib><creatorcontrib>Horiuchi, Seikoh</creatorcontrib><creatorcontrib>Kawakami, Masanobu</creatorcontrib><creatorcontrib>Kanazawa, Yasunori</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><jtitle>Diabetes research and clinical practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kakehashi, Akihiro</au><au>Inoda, Shigeru</au><au>Mameuda, Chiho</au><au>Kuroki, Masatoshi</au><au>Jono, Tadashi</au><au>Nagai, Ryuji</au><au>Horiuchi, Seikoh</au><au>Kawakami, Masanobu</au><au>Kanazawa, Yasunori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy</atitle><jtitle>Diabetes research and clinical practice</jtitle><addtitle>Diabetes Res Clin Pract</addtitle><date>2008-03-01</date><risdate>2008</risdate><volume>79</volume><issue>3</issue><spage>438</spage><epage>445</epage><pages>438-445</pages><issn>0168-8227</issn><eissn>1872-8227</eissn><abstract>Abstract Purpose We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. Methods Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. Results The mean VEGF and AGE levels in the vitreous (695.7 pg/ml and 2.4 mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9 pg/ml, p = 0.0007 and 1.3 mg/ml, p = 0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly ( r = 0.6; p = 0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. Conclusions By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18053608</pmid><doi>10.1016/j.diabres.2007.10.018</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult AGE Aged Aged, 80 and over Diabetes Diabetic retinopathy Diabetic Retinopathy - metabolism Diabetic Retinopathy - pathology Endocrinology & Metabolism Enzyme-Linked Immunosorbent Assay Female Glycation End Products, Advanced - metabolism Humans Immunohistochemistry Macrophage Macrophages - pathology Male Middle Aged Receptors, Vascular Endothelial Growth Factor - metabolism Vascular Endothelial Growth Factor A - metabolism VEGF VEGF receptor |
| title | Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy |
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