Effects of betaxolol on light responses and membrane conductance in retinal ganglion cells

PURPOSE. To examine the physiological effects of betaxolol, a beta(1)-adren ergic receptor blocker commonly used in the treatment of glaucoma, on retin al ganglion cells and to evaluate its potential to elicit responses consist ent with a neuroprotective agent against ganglion cell degeneration. METHODS. Single-unit extracellular recording, electroretinogram (ERG), intr acellular and whole-cell patch-clamp recording techniques were made from fl atmounted, isolated retina, superfused eye-cup, and living retinal slice pr eparations of the larval tiger salamander. RESULTS. Bath application of 20 mu M betaxolol reduced the glutamate-induce d increase of spontaneous spike rate in retinal ganglion cell by approximat ely 30%. The glutamate-induced postsynaptic current recorded under voltage- clamp conditions was reduced by 50 mu M betaxolol, and the difference curre nt-voltage (I-V) relation (I-Control -I-Betaxolol) was N-shaped and AP5-sen sitive, characteristic of N-methyl-D-aspartate receptor-mediated current. A pplication of 50 mu M betaxolol reversibly reduced the voltage-gated sodium and calcium currents by approximately one third of their peak amplitudes. The times-to-action of betaxolol on ganglion cells are long (15-35 minutes for 20-50 mu M betaxolol), indicative of modulation through slow biochemica l cascades. Betaxolol, up to 100 mu M, exerted no effects on horizontal cel ls or the ERG, suggesting that the primary actions of this beta(1) blocker are restricted to retinal ganglion cells. CONCLUSIONS. These physiological experiments provide supporting evidence th at betaxolol acts in a manner consistent with preventing retinal ganglion c ell death induced by elevated extracellular glutamate or by increased spont aneous spike: rates under pathologic conditions. The physiological actions of betaxolol lead to reducing neurotoxic effects in ganglion cells, which a re the most susceptible retinal neurons to glutamate-induced damages under ischemic and glaucomatous conditions. Therefore, betaxolol has the potentia l to be a neuroprotective agent against retinal degeneration in patients wi th disorders mediated by such mechanisms.