Role Of Long Non-coding RNA-MIAT In Ocular Neurovascular Dysfunction

Objective:Although nervous and vascular systems are functionally different,they usually share similar mechanisms for function maintenance.Neurovascular dysfunction has become the pathogenesis of several vascular and nervous disorders.This study was conducted to elucidate the role of long non-coding RNA-MIAT in ocular neurovascular dysfunction and its potential mechanism.Methods:The change of expression pattern of MIAT was detected by qRT-PCRs in animal models of vascular and neural diseases and retinal vascular and nervous cells in response to hyperoxia or hypoxia stress to clarify the correlation between MIAT and neurovascular dysfunction.In vivo,we revealed the role of MIAT in ocular neurovascular dysfunction by IB4 staining,slit lamp and immunofluorescences staining in the mouse models of retinal vascularization development,corneal neovascularization(CNV)and diabetic retinopathy(DR),respectively.In vitro,we employed MTT assay,hoechst staining,JC-1 staining,PI/Calcein-AM staining and immunofluorescence staining Ki-67 to study the impact of MIAT knockdown in retinal cell functions,such as vitality,proliferation,apoptosis and the interaction among retinal cells.Mechanistically,luciferase assay and qRT-PCRs were conducted to reveal the underlying mechanism of MIAT,which regulated Muller cell function.Results:The expression pattern of MIAT was abnormal in the animal models of oxygen-induced retinopathy(OIR),optic nerve transection(ONT)and diabetes mellitus as well as in Muller cells,endothelial cells,pericytes and neurons in response to hyperoxia or hypoxia stress,especially in Muller cells.In vivo,MIAT knockdown delayed the development of retinal vasculature in postnatal mice,decreased alkali-burn-induced angiogenesis in CNV model and attenuated the reactive gliosis and RGCs survival in diabetic mice.In vitro,MIAT knockdown decreased Muller cells and RGCs viability,mitochondrial depolarization and proliferation,whereas promoted apoptosis.Muller cells co-culture showed that MIAT knockdown in Muller cells influenced retinal neurons and endothelial cells function indirectly.Mechanistically,luciferase assay and qRT-PCRs revealed that MIAT regulated Muller cell function through MIAT/miR-150-5P/VEGF,subsequently mediated ocular neurovascular interaction.Conclusions:This study underscores that long non-coding RNA-MIAT is a common regulator of ocular nervous and vascular diseases.MIAT regulates retinal cells through MIAT/miR-150-5P/VEGF.MIAT may represent a new therapeutic target for treating neurovascular dysfunction.