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Y.–N. Chen, H. Yamada, M. Aihara, M. Araie; Neuroprotective Effect of Beta–adrenergic blockers on Hypoxic Damage in Purified Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2077.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To evaluate the neuroprotective effect of betaxolol, nipradilol and timolol, all beta–adrenergic antagonists, on hypoxia–induced cell death in rat purified retinal ganglion cells. Methods:Purified retinal ganglion cell (RGC) cultures were obtained from rat fetal retina utilizing the two–step immuno–panning procedure. The RGCs were cultured in serum–free medium. With the final drug concentrations of 10–8M,10–7M, and 10–6M, betaxolol, nipradilol and timolol were added in each medium and RGCs were incubated under hypoxic condition(5% O2, 5%CO2, 37°C) for 12 hours. Using the calcein–AM assay, the numbers of the viable cells were counted and the cell viabilities were calculated. The effect of each drug on hypoxia–induced change of intracellular calcium concentration was also evaluated by calcium–imagining techniques. Results:The viability of RGC cultures after 12 hours of hypoxia was 51.5% without drug treatment. The viability increased in a dose dependent fashion with exposure to betaxolol (10–8M: 51.5%; NS, 10–7M: 58.3%; p<0.05, 10–6M: 60.5%; p<0.05, n=7), nipradilol (10–8M: 57.4%; p<0.05, 10–7M: 58.8%; p<0.05, 10–6M: 60.5%; p<0.05, n=7) and timolol (10–8M: 55.0%; NS, 10–7M: 57.1%; p<0.05, 10–6M: 58.0%; p<0.05, n=7). There was no significant effect on hypoxia–induced intracellular calcium change. Conclusions:Betaxolol, nipradilol and timolol all have the protective effect against hypoxia–induced cell death in the purified retinal ganglion cells. It is supposed that the beta–blockers may exert anti–glaucoma effect on RGCs not only by reduction of intraocular pressure, but also by direct protection of hypoxia–induced RGC death.
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