title: mTOR inhibition attenuates glucose deprivation-induced death in photoreceptors via suppressing a mitochondria-dependent apoptotic pathway.
abstract: Acute energy depletion contributes to ischemia-induced retinal neuronal injury, causing photoreceptor death and subsequent vision loss. The mTOR pathway is a crucial cellular signaling hub modulating RNA transcription, protein synthesis, and metabolic balance. Thus, we mimicked acute energy depletion in photoreceptor cells (661W cells) with glucose deprivation and investigated neuroprotective mechanisms of mTOR inhibition. We found that treatment with rapamycin, an mTOR-specific inhibitor, reduced intracellular ROS, maintained the mitochondrial membrane potential and restored mitochondrial dysfunction. In addition, inhibiting the mTOR signal suppressed DRP1 translocation to the mitochondria, pro-apoptotic mitochondrial protein release, and caspase 3 activation when glucose was deprived. Inhibition of mTOR offers significant neuroprotection against glucose deprivation-induced injury in 661W cells, chiefly via suppressing mitochondrial-dependent pathways. These observations may shed light on treating ischemia-related retinal diseases.
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, ChangChun 130041, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Fan
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, ChangChun 130041, China.
authors.forename: Fu-Qaing
authors.initials: FQ
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, ChangChun 130041, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Ophthalmology, Second Hospital of Jilin University, ChangChun 130041, China. Electronic address: liguangyu@aliyun.com.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D020123:Sirolimus
keywords: DRP1; Mitochondrial membrane potential; Oxidative stress; Photoreceptor cells; Rapamycin; mTOR