PMID- 31274018 OWN - NLM STAT- MEDLINE DCOM- 20210615 LR - 20211204 IS - 1744-4160 (Electronic) IS - 1381-3455 (Linking) VI - 127 IP - 1 DP - 2021 Feb TI - Role of mammalian target of rapamycin in regulating HIF-1alpha and vascular endothelial growth factor signals in glaucoma. PG - 44-50 LID - 10.1080/13813455.2019.1609996 [doi] AB - Hypoxia inducible factor subtype 1alpha (HIF-1alpha) 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-1alpha 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-1alpha, VEGF and mTOR in retinal tissues of eyes with high intraocular pressure. In results, HIF-1alpha, 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-1alpha-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-1alpha-VEGF mechanism. FAU - Zhou, Jinzi AU - Zhou J AD - Department of Ophthalmology, The First People's Hospital of Guiyang, Guiyang, China. FAU - Chen, Fenghua AU - Chen F AD - Department of Ophthalmology, The First People's Hospital of Guiyang, Guiyang, China. FAU - Yan, Aimin AU - Yan A AD - Department of Ophthalmology, The First People's Hospital of Guiyang, Guiyang, China. FAU - Xia, Xiaobo AU - Xia X AD - Department of Ophthalmology, Xiangya Hospital of Central South University, Changsha, China. LA - eng PT - Journal Article DEP - 20190705 PL - England TA - Arch Physiol Biochem JT - Archives of physiology and biochemistry JID - 9510153 RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Caspase 3/metabolism MH - *Gene Expression Regulation MH - Glaucoma/*metabolism MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Intraocular Pressure MH - Male MH - Phosphorylation MH - Rats MH - Rats, Sprague-Dawley MH - Retina/metabolism MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/*metabolism MH - Vascular Endothelial Growth Factor A/*metabolism MH - Vascular Endothelial Growth Factor Receptor-2/metabolism OTO - NOTNLM OT - HIF-1alpha OT - VEGF OT - glaucoma OT - mTOR EDAT- 2019/07/06 06:00 MHDA- 2021/06/16 06:00 CRDT- 2019/07/06 06:00 PHST- 2019/07/06 06:00 [pubmed] PHST- 2021/06/16 06:00 [medline] PHST- 2019/07/06 06:00 [entrez] AID - 10.1080/13813455.2019.1609996 [doi] PST - ppublish SO - Arch Physiol Biochem. 2021 Feb;127(1):44-50. doi: 10.1080/13813455.2019.1609996. Epub 2019 Jul 5.