Invited review: Neuroprotective properties of certain beta-adrenoceptor antagonists used for the treatment of glaucoma.
Although it is known that ganglion cell death causes loss of vision in glaucoma, the pathogenesis of the disease is complex, probably involving an initial ischemic insult to the ganglion cell axons and glial cells with the ganglion cell bodies eventually being affected. It may therefore be necessary to blunt many stages in the pathogenesis of the disease to obtain a clinically effective neuroprotective strategy. In animal experiments, one cause of ganglion cell death in ischemia is an overactivation of glutamate receptors and a subsequent rise in intracellular levels of sodium and calcium ions as well as a generation of reactive oxygen species. In contrast, optic nerve death in ischemia is mainly caused by an influx of sodium and reversal of the sodium/calcium exchanger, which leads to a rise in intracellular calcium. Thus, a substance that reduces the influx of sodium will protect the ganglion cell axon, and if it also reduces calcium influx and/or acts as an antioxidant it will protect the ganglion cell body in addition. Of all antiglaucoma drugs, only beta-blockers have both calcium and sodium channel blocking activity, with betaxolol being the most efficacious of those analyzed. In addition, of the tested ophthalmic beta-blockers only metipranolol has powerful antioxidant properties. Moreover, laboratory studies on rats have shown that topically applied beta-blockers attenuate ischemic injury to ganglion cells by mechanisms that do not appear to involve an action on beta-receptors. Thus, of the substances used to lower intraocular pressure in glaucoma, beta-blockers have unique additional characteristics that also give them the capacity to act as neuroprotectants.
Osborne
Neville N
NN
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, United Kingdom. neville.osborne@eye.ox.ac.uk
Wood
John P M
JP
Chidlow
Glyn
G
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D018696:Neuroprotective Agents