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Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats
Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal altera...
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Published in: | Journal of pineal research 2013-03, Vol.54 (2), p.179-189 |
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creator | Salido, Ezequiel M. Bordone, Melina De Laurentiis, Andrea Chianelli, Mónica Keller Sarmiento, María Inés Dorfman, Damián Rosenstein, Ruth E. |
description | Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose‐enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a‐wave, b‐wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes. |
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We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose‐enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a‐wave, b‐wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.</description><identifier>ISSN: 0742-3098</identifier><identifier>EISSN: 1600-079X</identifier><identifier>DOI: 10.1111/jpi.12008</identifier><identifier>PMID: 22946773</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Animals ; Catalase - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; diabetic retinopathy ; Diabetic Retinopathy - drug therapy ; Diabetic Retinopathy - metabolism ; Electroretinography ; experimental type 2 diabetes mellitus ; Glucose - metabolism ; Immunohistochemistry ; Male ; melatonin ; Melatonin - therapeutic use ; Rats ; Rats, Wistar ; Thiobarbiturates - metabolism ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Journal of pineal research, 2013-03, Vol.54 (2), p.179-189</ispartof><rights>2012 John Wiley & Sons A/S</rights><rights>2012 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4318-2ba20bab0db497544a45b3be11ff06f1c1f95c08c2a44668534abc5846d63e7c3</citedby><cites>FETCH-LOGICAL-c4318-2ba20bab0db497544a45b3be11ff06f1c1f95c08c2a44668534abc5846d63e7c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22946773$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salido, Ezequiel M.</creatorcontrib><creatorcontrib>Bordone, Melina</creatorcontrib><creatorcontrib>De Laurentiis, Andrea</creatorcontrib><creatorcontrib>Chianelli, Mónica</creatorcontrib><creatorcontrib>Keller Sarmiento, María Inés</creatorcontrib><creatorcontrib>Dorfman, Damián</creatorcontrib><creatorcontrib>Rosenstein, Ruth E.</creatorcontrib><title>Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats</title><title>Journal of pineal research</title><addtitle>J. Pineal Res</addtitle><description>Diabetic retinopathy (DR) is a leading cause of acquired blindness in adults, mostly affected by type 2 diabetes mellitus (T2DM). We have developed an experimental model of early T2DM in adult rats which mimics some features of human T2DM at its initial stages and provokes significant retinal alterations. The aim of this work was to analyze the effect of melatonin on retinal changes induced by the moderate metabolic derangement. For this purpose, adult male Wistar rats received a control diet or 30% sucrose in the drinking water. Three weeks after this treatment, animals were injected with vehicle or streptozotocin (STZ, 25 mg/kg). One day or 3 wk after vehicle or STZ injection, animals were subcutaneously implanted with a pellet of melatonin. Fasting and postprandial glycemia, and glucose, and insulin tolerance tests were analyzed. At 12 wk of treatment, animals which received a sucrose‐enriched diet and STZ showed significant differences in metabolic tests, as compared with control groups. Melatonin, which did not affect glucose metabolism in control or diabetic rats, prevented the decrease in the electroretinogram a‐wave, b‐wave, and oscillatory potential amplitude, and the increase in retinal lipid peroxidation, NOS activity, TNFα, Müller cells glial fibrillary acidic protein, and vascular endothelial growth factor levels. In addition, melatonin prevented the decrease in retinal catalase activity. These results indicate that melatonin protected the retina from the alterations observed in an experimental model of DR associated with type 2 diabetes.</description><subject>Animals</subject><subject>Catalase - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>diabetic retinopathy</subject><subject>Diabetic Retinopathy - drug therapy</subject><subject>Diabetic Retinopathy - metabolism</subject><subject>Electroretinography</subject><subject>experimental type 2 diabetes mellitus</subject><subject>Glucose - metabolism</subject><subject>Immunohistochemistry</subject><subject>Male</subject><subject>melatonin</subject><subject>Melatonin - therapeutic use</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Thiobarbiturates - metabolism</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0742-3098</issn><issn>1600-079X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNqFkUtv1TAQRi0Eope2C_4A8hIWaf12skQX-kAFWqlV2VkTZ1Jc8iJOSvPv8e1tu0OMLI2lOXOk0UfIW84OeKrD2yEccMFY_oKsuGEsY7b48ZKsmFUik6zId8ibGG9ZIvLcvCY7QhTKWCtX5O7yJ44w4DwFT7Gugwe_0L6mLTYw9V3oaHojVrMP3U36TKGDhlbQwg1uRtBRvB9wDC12U5q0fYXNRoAwNgudlgGpoFWAEieMDzKY4h55VUMTcf-x75Kro8-X65Ps7Pvx6frjWeaV5HkmShCshJJVpSqsVgqULmWJnNc1MzX3vC60Z7kXoJQxuZYKSq9zZSoj0Xq5S95vvcPY_54xTq4N0WPTQIf9HB2XXBshmdX_R0WuldHcmoR-2KJ-7GMcsXZDuh_GxXHmNom4lIh7SCSx7x61c9li9Uw-RZCAwy3wJzS4_NvkvpyfPimz7UaIE94_b8D4yxkrrXbX347dp6_rkwt2ce6s_Au_6aSg</recordid><startdate>201303</startdate><enddate>201303</enddate><creator>Salido, Ezequiel M.</creator><creator>Bordone, Melina</creator><creator>De Laurentiis, Andrea</creator><creator>Chianelli, Mónica</creator><creator>Keller Sarmiento, María Inés</creator><creator>Dorfman, Damián</creator><creator>Rosenstein, Ruth E.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7TK</scope></search><sort><creationdate>201303</creationdate><title>Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats</title><author>Salido, Ezequiel M. ; Bordone, Melina ; De Laurentiis, Andrea ; Chianelli, Mónica ; Keller Sarmiento, María Inés ; Dorfman, Damián ; Rosenstein, Ruth E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4318-2ba20bab0db497544a45b3be11ff06f1c1f95c08c2a44668534abc5846d63e7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Catalase - metabolism</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>diabetic retinopathy</topic><topic>Diabetic Retinopathy - drug therapy</topic><topic>Diabetic Retinopathy - metabolism</topic><topic>Electroretinography</topic><topic>experimental type 2 diabetes mellitus</topic><topic>Glucose - metabolism</topic><topic>Immunohistochemistry</topic><topic>Male</topic><topic>melatonin</topic><topic>Melatonin - therapeutic use</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Thiobarbiturates - metabolism</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salido, Ezequiel M.</creatorcontrib><creatorcontrib>Bordone, Melina</creatorcontrib><creatorcontrib>De Laurentiis, Andrea</creatorcontrib><creatorcontrib>Chianelli, Mónica</creatorcontrib><creatorcontrib>Keller Sarmiento, María Inés</creatorcontrib><creatorcontrib>Dorfman, Damián</creatorcontrib><creatorcontrib>Rosenstein, Ruth E.</creatorcontrib><collection>Istex</collection><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>Neurosciences Abstracts</collection><jtitle>Journal of pineal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salido, Ezequiel M.</au><au>Bordone, Melina</au><au>De Laurentiis, Andrea</au><au>Chianelli, Mónica</au><au>Keller Sarmiento, María Inés</au><au>Dorfman, Damián</au><au>Rosenstein, Ruth E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats</atitle><jtitle>Journal of pineal research</jtitle><addtitle>J. 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subjects | Animals Catalase - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism diabetic retinopathy Diabetic Retinopathy - drug therapy Diabetic Retinopathy - metabolism Electroretinography experimental type 2 diabetes mellitus Glucose - metabolism Immunohistochemistry Male melatonin Melatonin - therapeutic use Rats Rats, Wistar Thiobarbiturates - metabolism Tumor Necrosis Factor-alpha - metabolism |
title | Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats |
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