ABSTRACT
Glaucoma is a progressive neurodegenerative disease, characterized by retinal ganglion cells (RGCs) and axon degeneration. The development of neuroprotective drug is required for improving the efficiency of glaucoma treatment. Eucommia ulmoides Oliv. has been used as a source of traditional medicine and as a beneficial health food. Lignans is one of the main bioactive components of Eucommia ulmoides. Here, we show that lignans protects RGCs against oxidative stress-induced injury in vitro. Moreover, lignans exerts neuroprotective effect on glaucoma-associated optic neuropathy in glaucomatous rats. Lignans treatment could improve oxidative stress response in RGCs and retinas of glaucomatous rats. Lignans plays an anti-oxidative stress role via the activation of AMPK signaling. This study provides evidence that lignans possesses protective effect on glaucoma-associated optic neuropathy. Lignans might be an alternative for the prevention and treatment of glaucomatous neurodegeneration.
Subject(s)
Eucommiaceae/chemistry , Glaucoma/complications , Lignans/therapeutic use , Neuroprotective Agents/therapeutic use , Optic Nerve Diseases/drug therapy , Optic Nerve Diseases/etiology , Animals , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Fluoresceins/metabolism , Gene Expression Regulation/drug effects , Glaucoma/drug therapy , Hydrogen Peroxide/pharmacology , Lignans/pharmacology , Male , Neuroprotective Agents/pharmacology , Phosphopyruvate Hydratase/metabolism , RNA, Long Noncoding/metabolism , Rats , Rats, Wistar , Retinal Ganglion Cells/drug effects , Signal Transduction/drug effects , Sincalide/metabolism , Tubulin/metabolismABSTRACT
Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications.
