Role of mammalian target of rapamycin in regulating HIF-1α and vascular endothelial growth factor signals in glaucoma

Abstract

Hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in the development of glaucoma. This study examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, vascular endothelial growth factor (VEGF). Glaucoma was induced by chronic elevation of intraocular pressure using laser burns in rats. ELISA and western blot analysis were employed to determine the levels of HIF-1α, VEGF and mTOR in retinal tissues of eyes with high intraocular pressure. In results, HIF-1α, VEGF and VEGF receptor subtype 2 were increased in laser eyes. The p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4, p70 ribosomal S6 protein kinase 1 were also amplified in retina of laser eyes. Blocking mTOR using rapamycin attenuated HIF-1α-VEGF pathways, accompanied with downregulation of apoptotic Caspase-3. Our data revealed potential signalling pathways engaged in the development of glaucoma, including the activation of mTOR and HIF-1α-VEGF mechanism.