| Glaucoma is a heterogeneous group of diseases characterised by cupping of the optic nerve head and visual-field damage.It’s the most frequent cause of irreversible blindness worldwide.The involvement of micro RNAs(mi Rs)has been implicated in regulating the complex biological responses to changes in intraocular pressure.However,the therapeutic role of mi R-200 a on glaucoma has not been well studied yet.Purpose: To investigate the effect of micro RNA-200 a in the retina using a well-established mice glaucoma model by regulating FGF7 and its related mechanism.It may provide a new target for treatment of glaucoma.Methods: First of all,microarray expression profiles were used to screen the glaucoma-related genes.FGF7 was selected as the follow-up gene.The relationship between mi R-200 a and FGF7 was validated by bioinformatics analysis and dual-luciferase reporter gene assay.Secondly,Glaucoma-related parameters were investigated in vivo and in vitro.They including the structure and morphology of retina,expression of CD11 b and i NOS,activation of Muller cells,and apoptosis of retinal ganglion cells(RGCs)in the mouse model were measured by HE staining,immunohistochemistry,MTT assay and TUNEL assay,respectively.At last,to confirm whether mi R-200 a suppressed the MAPK signaling pathway via downregulating FGF7.The m RNA changes of mi R-200 a,FGF7,MAPK signaling pathways(ERK,JNK,p38)were analyzed by Real-time quantitative real-time PCR(RT-q PCR).And The protein contents of FGF7,MAPK signaling pathways(ERK,JNK,p38,p-ERK,p-JNK,p-p38,),Bax,Bcl-2 were analyzed Western Blot respectively.Results: Mi R-200 a was reduced in the Retina of chronic ocular Hypertension mouse,whereas FGF7 was robustly induced.Thereby,we speculated that FGF7 was negatively regulated by mi R-200 a.Downregulated mi R-200 a could activate the MAPK signaling pathway following elevations in ERK,JNK,p38 and Bax expression and reduction in Bcl-2expression.In the Retina of chronic ocular Hypertension mouse,downregulated mi R-200 a increased the expression of CD11 b and i NOS and the apoptosis of RGCs,but stimulated the inactivation of Müller cells.However,the above-mentioned alternations induced by downregulated mi R-200 a were reversed after FGF7 repression.mi R-200 a can inhibit the FGF7-mediated MAPK signaling pathway.Conclusions: Our study demonstrated neuroprotective effects of overexpressed micro RNA-200 a on activation of glaucoma-related optic nerve damage via downregulating FGF7-mediated MAPK signaling pathway.It may provide a new target for treatment of glaucoma. |
