Neuroprotective Effects of Betaxolol Mediated by Heme Oxygenase-1 Induction in RGC-5

Abstract

Purpose: To evaluate the neuroprotective effects of betaxolol (betaxolol hydrochloride) under hypoxic conditions using retinal ganglion cells (RGC-5) and determine whether heme oxygenase-1 (HO-1) expression exerts cytoprotective effects. Methods: In this study, cultured RGC-5 cells were incubated with different concentrations of betaxolol hydrochloride (0.1 μM, 1 μM or 5 μM) and with 10 μM zinc protoporphyrin (ZnPP), in a hypoxia incubator (1% O2, 5% CO2, 94% N2) for 48 hours and the cell viability of each group was determined. Additionally, cell viability was measured after RGC-5 cells were incubated with 5 μM of brinzolamide (Azopt), brimonidine tartrate (Alphagan) or travoprost (Travatan). RGC-5 cells were divided into three groups and incubated under three different conditions, normoxia group (20% O2, 5% CO2), hypoxia group (1% O2, 5% CO2) and the group with 5 μM of Betoptic S treated under hypoxic conditions (hypoxia, Betoptic S). After incubation for 4, 8, 12 and 24 hours, HO-1 expression was analyzed using Western blotting. Results: Cell viability significantly increased in RGC-5 cells treated with Betoptic S compared with other antiglaucoma agents. Increased levels of HO-1 expression indicate its relevance in cell viability. Furthermore, increased RGC-5 cell viability by Betoptic S was significantly reduced in the HO-1 inhibitor ZnPP-treated group. Conclusions: We reaffirmed the known cytoprotective effects of Betoptic S and the results suggests that HO-1 expression exerts cytoprotective effects against hypoxia. J Korean Ophthalmol Soc 2016;57(1):113-119