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Animals were divided in five groups (<jats:italic>n<\/jats:italic>=8\/group); one group consisted of non\u2010diabetic rats as control, while the other four were diabetic animals either non\u2010treated or treated with <jats:bold>CAF6<\/jats:bold>, <jats:bold>CAF12<\/jats:bold> or resveratrol intravitreally for four weeks. Retinal superoxide dismutase (SOD) activity and 8\u2010<jats:italic>iso<\/jats:italic>\u2010prostaglandin F<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> (iPF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub>) levels were evaluated by an ELISA assay. Phosphorylation of ERK1\/2 and AKT was determined by immunoblotting in retinal homogenates. Retinal morphology was also examined using light microscopy. Treatment with <jats:bold>CAF6<\/jats:bold> and <jats:bold>CAF12<\/jats:bold> increased retinal SOD activity, while it decreased iPF<jats:sub>2<jats:italic>\u03b1<\/jats:italic><\/jats:sub> levels in diabetic rats. Phosphorylation of ERK1\/2 was increased, while AKT phosphorylation was decreased in diabetic rats compared to normal control and these alterations were significantly reversed in diabetic rats treated with <jats:bold>CAF6<\/jats:bold> and <jats:bold>CAF12<\/jats:bold>. Furthermore, thickness of the whole retinal layer, outer nuclear layer, and ganglion cell count were decreased in diabetic rats compared to control and <jats:bold>CAF6<\/jats:bold> and <jats:bold>CAF12<\/jats:bold> treatments prevented these changes. <jats:bold>CAF6<\/jats:bold> and <jats:bold>CAF12<\/jats:bold> seem to be effective agents for treatment of diabetic retinopathy via attenuation of retinal oxidative stress and improvement of neuronal survival signaling.<\/jats:p>","DOI":"10.1002\/cbdv.201900405","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T04:11:05Z","timestamp":1569903065000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Caffeic Acid Alkyl Amide Derivatives Ameliorate Oxidative Stress and Modulate ERK1\/2 and AKT Signaling Pathways in a Rat Model of Diabetic Retinopathy"],"prefix":"10.1002","volume":"16","author":[{"given":"Mohammad","family":"Fathalipour","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz 71348-45794 Iran"},{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz 71348-53734 Iran"}]},{"given":"Masoomeh","family":"Eghtedari","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Shiraz University of Medical Sciences  Shiraz 71348-14336 Iran"}]},{"given":"Fernanda","family":"Borges","sequence":"additional","affiliation":[{"name":"CIQUP\/Department of Chemistry and Biochemistry Faculty of Sciences, University of Porto  Porto 4169-007 Portugal"}]},{"given":"Tiago","family":"Silva","sequence":"additional","affiliation":[{"name":"CIQUP\/Department of Chemistry and Biochemistry Faculty of Sciences, University of Porto  Porto 4169-007 Portugal"}]},{"given":"Fatemeh","family":"Moosavi","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz 71348-53734 Iran"}]},{"given":"Omidreza","family":"Firuzi","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz 71348-53734 Iran"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-1174","authenticated-orcid":false,"given":"Hossein","family":"Mirkhani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz 71348-45794 Iran"},{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz 71348-53734 Iran"}]}],"member":"311","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.03.024"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/414813a"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4435-8"},{"key":"e_1_2_8_4_1","first-page":"300","article-title":"\u2018Alteration of growth factors and neuronal death in diabetic retinopathy: what we have learned so far\u2019","volume":"17","author":"Whitmire W.","year":"2011","journal-title":"Mol. 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