IN-VIVO AND IN-VITRO EXPERIMENTS SHOW THAT BETAXOLOL IS A RETINAL NEUROPROTECTIVE AGENT

The aim of the study was to determine whether betaxolol is a neuroprot ective agent and can therefore slow down the changes seen in the retin a following ischaemia/reperfusion. Ischaemia was induced in one rat ey e by raising the intraocular pressure for 45 min. Three days later ele ctroretinograms, were recorded from both eyes and the retinas were exa mined immunohistochemically for the localisation of calretinin and cho line acetyltransferase (ChAT) immunoreactivities. The effect of glutam ate agonists, hypoxia or experimental ischaemia was examined on the GA BA immunoreactivity, lactate dehydrogenase (LDH) and internal calcium levels ([Ca2+](i)) of the isolated rabbit retina, rat cortical culture s and chick retinal cell cultures respectively. Betaxolol was tested t o see whether it can attenuate the influence of the glutamate agonists , hypoxia or experimental ischaemia. Ischaemia for 45 min causes a cha nge in the nature of the normal calretinin immunoreactivity, an oblite ration of the ChAT immunoreactivity and a drastic reduction in the b-w ave of the electroretinogram after 3 days of reperfusion. When betaxol ol 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 re tinas incubated in vitro in physiological, solution lacking oxygen/glu cose or containing the glutamate agonists kainate or NMDA caused a cha nge in the nature of the GABA immunoreactivity, Inclusion of betaxolol partially prevented the changes caused by NMDA and lack of oxygen/glu cose. Rat cortical cultures exposed to glutamate or hypoxia/reoxygenat ion resulted in a release of LDH. The release of the enzyme was almost completely attenuated when betaxolol was included in the culture medi um. Kainate increased the [Ca2+](i) in chick retinal cultures, as meas ured with Indo-1. In a medium with sodium, this kainate-induced elevat ion 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. (C) 1997 Elsevi er Science B.V.