title: Melatonin-mediated cytoprotection against hyperglycemic injury in Müller cells.
abstract: Oxidative stress is a contributing factor to the development and progression of diabetic retinopathy, a leading cause of blindness in people at working age worldwide. Recent studies showed that Müller cells play key roles in diabetic retinopathy and produce vascular endothelial growth factor (VEGF) that regulates retinal vascular leakage and proliferation. Melatonin is a potent antioxidant capable of protecting variety of retinal cells from oxidative damage. In addition to the pineal gland, the retina produces melatonin. In the current study, we investigated whether melatonin protects against hyperglycemia-induced oxidative injury to Müller cells and explored the potential underlying mechanisms. Our results show that both melatonin membrane receptors, MT1 and MT2, are expressed in cultured primary Müller cells and are upregulated by elevated glucose levels. Both basal and high glucose-induced VEGF production was attenuated by melatonin treatment in a dose-dependent manner. Furthermore, we found that melatonin is a potent activator of Akt in Müller cells. Our findings suggest that in addition to functioning as a direct free radical scavenger, melatonin can elicit cellular signaling pathways that are protective against retinal injury during diabetic retinopathy.
authors.affiliation: The Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Jiang
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: Zhenyang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Saimei
authors.initials: S
authors.lastname: Yan
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Jiyang
authors.initials: J
authors.lastname: Cai
authors.forename: Gezhi
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006943:Hyperglycemia / Q000517:prevention & control*; D008550:Melatonin / Q000502:physiology*; D009457:Neuroglia / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017931:DNA Primers; D008550:Melatonin