title: In vivo and in vitro experiments show that betaxolol is a retinal neuroprotective agent.
abstract: The aim of the study was to determine whether betaxolol is a neuroprotective agent and can therefore slow down the changes seen in the retina following ischaemia/reperfusion. Ischaemia was induced in one rat eye by raising the intraocular pressure for 45 min. Three days later electroretinograms were recorded from both eyes and the retinas were examined immunohistochemically for the localisation of calretinin and choline acetyltransferase (ChAT) immunoreactivities. The effect of glutamate agonists, hypoxia or experimental ischaemia was examined on the GABA immunoreactivity, lactate dehydrogenase (LDH) and internal calcium levels ([Ca2+]i) of the isolated rabbit retina, rat cortical cultures and chick retinal cell cultures respectively. Betaxolol was tested to see whether it can attenuate the influence of the glutamate agonists, hypoxia or experimental ischaemia. Ischaemia for 45 min causes a change in the nature of the normal calretinin immunoreactivity, an obliteration of the ChAT immunoreactivity and a drastic reduction in the b-wave of the electroretinogram after 3 days of reperfusion. When betaxolol was injected i.p. into the rats before ischaemia and on the days of reperfusion the changes to the calretinin and ChAT immunoreactivities were reduced and the reduction of the b-wave was prevented. Rabbit retinas incubated in vitro in physiological solution lacking oxygen/glucose or containing the glutamate agonists kainate or NMDA caused a change in the nature of the GABA immunoreactivity. Inclusion of betaxolol partially prevented the changes caused by NMDA and lack of oxygen/glucose. Rat cortical cultures exposed to glutamate or hypoxia/reoxygenation resulted in a release of LDH. The release of the enzyme was almost completely attenuated when betaxolol was included in the culture medium. Kainate increased the [Ca2+]i in chick retinal cultures, as measured with Indo-1. In a medium with sodium, this kainate-induced elevation of [Ca2+]i was significantly reduced by betaxolol. The combined data show that betaxolol is a neuroprotective agent and attenuates the effects on the retina induced by raising the intraocular pressure to simulate an ischaemic insult as may occur in glaucoma.
authors.affiliation: Nuffield Laboratory of Ophthalmology, Oxford University, UK.
authors.forename: N N
authors.initials: NN
authors.lastname: Osborne
authors.forename: C
authors.initials: C
authors.lastname: Cazevieille
authors.forename: A L
authors.initials: AL
authors.lastname: Carvalho
authors.forename: A K
authors.initials: AK
authors.lastname: Larsen
authors.forename: L
authors.initials: L
authors.lastname: DeSantis
mesh_terms: D000818:Animals; D015784:Betaxolol / Q000494:pharmacology*; D064032:Calbindin 2; D002118:Calcium / Q000032:analysis; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured / Q000737:chemistry / Q000201:enzymology; D002642:Chick Embryo; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004596:Electroretinography; D005123:Eye / Q000098:blood supply; D005136:Eye Proteins / Q000032:analysis; D018698:Glutamic Acid / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000188:drug therapy; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D013565:Sympatholytics / Q000494:pharmacology*
chemical_list: C576512:Calb2 protein, rat; D064032:Calbindin 2; D005136:Eye Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D064030:S100 Calcium Binding Protein G; D013565:Sympatholytics; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D002795:Choline O-Acetyltransferase; D015784:Betaxolol; D010100:Oxygen; D002118:Calcium