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Lipid peroxidation (<jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content>), glutathione (<jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content>), tumor necrosis factor\u2010\u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1) and interleukin\u20101\u03b2 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2) concentrations, expression of vascular endothelial growth factor receptors, <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lt\u20101 and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lk\u20101, release of cytochrome <jats:italic>c<\/jats:italic> from mitochondria, and caspase\u20103 expression were examined in the retinas of 1\u2010day\u2010old rats at 3\u00a0hr to 14\u00a0days after a hypoxic exposure. The m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and protein expression of <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lt\u20101 and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lk\u20101 and the tissue concentration of <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TNF<\/jats:styled-content>\u2010\u03b1, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 were upregulated significantly after the hypoxic exposure, whereas the content of <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content> was decreased significantly. <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content> cultures also showed increased <jats:styled-content style=\"fixed-case\">LPO<\/jats:styled-content> and decreased <jats:styled-content style=\"fixed-case\">GSH<\/jats:styled-content> levels after hypoxic exposure but these effects were reversed in cells treated with melatonin. <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1 and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 expression was specifically located on microglial cells, whereas <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lt\u20101 and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lk\u20101 was limited to <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s as confirmed by double immunofluorescence labeling. Cultures of hypoxic microglial cells treated with melatonin showed a significant reduction in the release of these cytokines as compared to untreated hypoxic cells. Hypoxia induced increase in the cytosolic cytochrome <jats:italic>c<\/jats:italic> and caspase\u20103 in <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s was attenuated with melatonin treatment. The results suggest that, in hypoxic injuries, melatonin is neuroprotective to <jats:styled-content style=\"fixed-case\">RGC<\/jats:styled-content>s in the developing retina through its antioxidative, anti\u2010inflammatory, and anti\u2010apoptotic effects. Melatonin suppressed <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lt\u20101 and <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>lk\u20101 expression in retinal blood vessels, which may result in reduced retinal vascular permeability and it also preserved mitochondrial function as shown by a reduction in cytochrome <jats:italic>c<\/jats:italic> leakage into the cytosol. The results may have therapeutic implications for the management of retinopathy of prematurity.<\/jats:p>","DOI":"10.1111\/jpi.12016","type":"journal-article","created":{"date-parts":[[2012,9,11]],"date-time":"2012-09-11T17:30:29Z","timestamp":1347384629000},"page":"190-206","source":"Crossref","is-referenced-by-count":60,"title":["Neuroprotective effect of melatonin against hypoxia\u2010induced retinal ganglion cell death in neonatal rats"],"prefix":"10.1111","volume":"54","author":[{"given":"Charanjit","family":"Kaur","sequence":"first","affiliation":[{"name":"Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viswanathan","family":"Sivakumar","sequence":"additional","affiliation":[{"name":"Department of Anatomy Yong Loo Lin School of Medicine National University of Singapore Singapore 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