Effects of betaxolol on light responses and membrane conductance in retinal ganglion cells.
OBJECTIVE
To examine the physiological effects of betaxolol, a beta1-adrenergic receptor blocker commonly used in the treatment of glaucoma, on retinal ganglion cells and to evaluate its potential to elicit responses consistent with a neuroprotective agent against ganglion cell degeneration.


METHODS
Single-unit extracellular recording, electroretinogram (ERG), intracellular and whole-cell patch-clamp recording techniques were made from flatmounted, isolated retina, superfused eyecup, and living retinal slice preparations of the larval tiger salamander.


RESULTS
Bath application of 20 microM betaxolol reduced the glutamate-induced increase of spontaneous spike rate in retinal ganglion cell by approximately 30%. The glutamate-induced postsynaptic current recorded under voltage-clamp conditions was reduced by 50 microM betaxolol, and the difference current-voltage (I-V) relation (I(Control)-I(betaxolol)) was N-shaped and AP5-sensitive, characteristic of N-methyl-D-aspartate receptor-mediated current. Application of 50 microM 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 microM betaxolol), indicative of modulation through slow biochemical cascades. Betaxolol, up to 100 microM, exerted no effects on horizontal cells or the ERG, suggesting that the primary actions of this beta1 blocker are restricted to retinal ganglion cells.


CONCLUSIONS
These physiological experiments provide supporting evidence that betaxolol acts in a manner consistent with preventing retinal ganglion cell death induced by elevated extracellular glutamate or by increased spontaneous spike rates under pathologic conditions. The physiological actions of betaxolol lead to reducing neurotoxic effects in ganglion cells, which are the most susceptible retinal neurons to glutamate-induced damages under ischemic and glaucomatous conditions. Therefore, betaxolol has the potential to be a neuroprotective agent against retinal degeneration in patients with disorders mediated by such mechanisms.
Gross
R L
RL
Cullen Eye Institute, Baylor College of Medicine, Houston, Texas 77030-2707, USA. rgross@bcm.tmc.edu
Hensley
S H
SH
Gao
F
F
Yang
X L
XL
Dai
S C
SC
Wu
S M
SM
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000557:Ambystoma; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D015784:Betaxolol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004596:Electroretinography; D018698:Glutamic Acid / Q000494:pharmacology; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001224:Aspartic Acid; D018698:Glutamic Acid; D012964:Sodium; D015784:Betaxolol; D002118:Calcium