Effects of beta-adrenergic blockers on glutamate-induced calcium signals in adult mouse retinal ganglion cells.
Betaxolol, a selective beta(1)-adrenoceptor antagonist, is an antiglaucoma drug commonly used to lower the intraocular pressure (IOP) in treatment of glaucoma. Recent evidence has also shown that it attenuates ligand- and voltage-gated currents in retinal ganglion cells, which may lead to reduction of intracellular calcium and prevention of glutamate-induced ganglion cell damage in glaucoma. In the present study, we examined the effectiveness of betaxolol and other beta-adrenergic blockers on glutamate-induced calcium signals. Dissociated adult mouse retinal ganglion cells were immuno-labeled with antibody CD90.2 and loaded with Fura-2AM. Calcium signals were recorded with optical recording techniques. Low doses of glutamate cause an increase in intracellular calcium that may result in pathological changes in ganglion cells. The action of glutamate could be reversibly suppressed by beta-adrenergic blockers and the order of inhibitory potency is (s)(-)-propranolol>betaxolol>>timolol, with average IC(50) of 78.05, 235.7 and 2167.05, microM, respectively. Betaxolol compressed the dose-response curve of glutamate. The EC(50) of glutamate was shifted from 6.19 to 23.53 microM, indicating that betaxolol acts as a non-competitive inhibitor of glutamate response in retinal ganglion cells. Our data are consistent with previous reports that betaxolol and other beta-adrenergic blockers may exert its neuroprotective action by suppression of glutamate-induced intracellular calcium increase in retinal ganglion cells.
Zhang
Jian
J
Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, One Baylor Plaza, 6565 Fannin Street, NC-205, Houston, TX 77030, USA.
Wu
Samuel M
SM
Gross
Ronald L
RL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies; D015784:Betaxolol / Q000494:pharmacology; D002118:Calcium / Q000032:analysis; D018698:Glutamic Acid / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018800:Thy-1 Antigens / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000906:Antibodies; D018800:Thy-1 Antigens; D018698:Glutamic Acid; D015784:Betaxolol; D002118:Calcium