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Neuroprotective effect of melatonin against hypoxia-induced retinal ganglion cell death in neonatal rats.

Abstract：

:The purpose of this study was to determine whether melatonin treatment would mitigate retinal ganglion cell (RGC) death in the developing retina following a hypoxic insult. Lipid peroxidation (LPO), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations, expression of vascular endothelial growth factor receptors, Flt-1 and Flk-1, release of cytochrome c from mitochondria, and caspase-3 expression were examined in the retinas of 1-day-old rats at 3 hr to 14 days after a hypoxic exposure. The mRNA and protein expression of Flt-1 and Flk-1 and the tissue concentration of LPO, TNF-α, and IL-1β were upregulated significantly after the hypoxic exposure, whereas the content of GSH was decreased significantly. RGC cultures also showed increased LPO and decreased GSH levels after hypoxic exposure but these effects were reversed in cells treated with melatonin. TNF-α and IL-1β expression was specifically located on microglial cells, whereas Flt-1 and Flk-1 was limited to RGCs 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 c and caspase-3 in RGCs was attenuated with melatonin treatment. The results suggest that, in hypoxic injuries, melatonin is neuroprotective to RGCs in the developing retina through its antioxidative, anti-inflammatory, and anti-apoptotic effects. Melatonin suppressed Flt-1 and Flk-1 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 c leakage into the cytosol. The results may have therapeutic implications for the management of retinopathy of prematurity.

journal_name

J Pineal Res

journal_title

Journal of pineal research

authors

Kaur C,Sivakumar V,Robinson R,Foulds WS,Luu CD,Ling EA

doi

10.1111/jpi.12016

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

190-206

issue

eissn

0742-3098

issn

1600-079X

journal_volume

pub_type

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Neuroprotective effect of melatonin against hypoxia-induced retinal ganglion cell death in neonatal rats.