Intraocular miR-211 exacerbates pressure-induced cell death in retinal ganglion cells via direct repression of FRS2 signaling

摘要: Abstract MicroRNAs (miRNAs) are emerging as important regulators of neurodegenerative diseases. However, research into ocular intracellular miRNAs, though possessing great potential to uncover novel and valuable therapeutic targets for glaucoma, is only at an early stage. Here we show that expression levels miR-211 were significantly induced in aqueous humor (AH) samples from patients with glaucoma when compared normal AH samples. Notably, oxidative stress-elicited potentiated high pressure-induced retinal ganglion cells (RGCs) death by impairing ERK activation but enhancing P38 activation, effect mediated direct downregulation fibroblast growth factor receptor substrate 2 (Frs2) signaling pathway a sequence complementarity-dependent fashion. In support the concept fundamental connection between upregulation augmented cell RGCs, showed ectopic exogenous FRS2 was sufficient neutralize miR-211-induced decrease viability improved miR-211-inhibited survival, pressure-challenged RGC-5 cells. Together, our findings negatively modulates survival programs upon pressure challenge regulating Frs2 signaling, they define roles miR-211/Frs2 cascade regulatory feedback loop mediates pathogenesis glaucoma.