title: Neuroprotective Effect of Ocular Hypotensive Drugs: Latanoprost/Timolol in Combination Are More Effective than Each as Monotherapy in RGC-5.
abstract: The combination of timolol and latanoprost, which are ocular hypotensive agents, has a greater ocular hypotensive effect than each as monotherapy. However, the protective effect of the combination is not well understood. In the present study, we investigated whether latanoprost/timolol in combination has an additive or synergistic cytoprotective effect on neuro retinal cells (RGC-5). To investigate the protective effects of timolol/latanoprost in combination, cultured RGC-5 were treated with various concentrations of these two agents, singly or together, after which the cells were exposed to oxidative stress, serum deprivation, or endoplasmic reticulum (ER) stress in vitro. Cells were also treated with an Akt inhibitor, LY294002, to examine the mechanism of the protective effect. Latanoprost, timolol, and the two in combination reduced cell death induced by oxidative stress, serum deprivation, or ER stress. The latanoprost/timolol combination reduced cell death to a greater extent than monotherapy with latanoprost or timolol on serum deprivation only, and LY294002 inhibited the protective effect of their combination. These findings suggest that timolol/latanoprost in combination have a protective effect against serum deprivation only by activation of Akt signaling. Furthermore, this combination has not only an ocular hypotensive effect but also a neuroprotective effect.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fuma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Imamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanno
authors.forename: Norihito
authors.initials: N
authors.lastname: Takano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D000077338:Latanoprost; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D012160:Retina / Q000166:cytology*; D013999:Timolol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol