advertisement
Abstract #15513 Published in IGR 1-3
Topically applied betaxolol attenuates NMDA-induced toxicity to ganglion cells and the effects of ischaemia to the retina
Osborne NN; DeSantis L; Bae JH; Ugarte M; Wood JPM; Nash MS; Chidlow GExperimental Eye Research 1999; 69: 331-342
The present results show that topically applied Betoptic® (0.5% betaxolol) to the rabbit or rat eye reaches the retina and can counteract the detrimental effects caused by ischemia/reperfusion or N-methyl-D-aspartate (NMDA)-induced insults to the retina. Betaxolol is a 1-adrenergic blocker but its neuroprotective action is generally thought to be due to its calcium channel blocking properties. Support for this view comes from studies on cultures of cortical neurons where it was found that betaxolol attenuated the NMDA-induced influx of 45Ca2+, while adrenoreceptor agonists were ineffective. Topically applied Betoptic® to the rabbit eye was observed to reach the retina in maximal amounts within 60 minutes. Some of the substance was also found in the contralateral retina of the untreated eye suggesting that the agent reaches the retina by local systemic and retinal circulation. Concurrent treatment with Latanoprost® did not result in a greater amount of betaxolol reaching the retina. An ophthalmodynamometric procedure, which raises the intraocular pressure, was used to apply an ischemic insult to the rabbit retina. After three days of reperfusion, the b-wave of the electroretinogram was reduced by an average of 59% and the choline acetyltransferase immunoreactivity in the retina was almost obliterated. However, when experiments were carried out on animals which had been treated with one drop of Betoptic® twice daily for four weeks before ischemia and also during the reperfusion phase, the reductions in both the b-wave of the electroretinogram and retinal choline acetyltransferase immunoreactivity due to ischemia/reperfusion, were greatly attenuated. Intravitreal injection of NMDA into the rat eye caused a decrease in the immunostaining for Thy-1 antigen which is associated with ganglion cells. The Thy-1 mRNA level was also reduced as was the mRNA for the common subunit of the NMDA receptor, the NR1 subunit. However, in animals subjected to a topical Betoptic® regime, before and after intravitreal injection of NMDA, the decreases in the mRNA levels of Thy-1 and NR1 were significantly attenuated.
Dr. N.N. Osborne, Nuffield Laboratory of Ophthalmology, Oxford University, Walton Street, Oxford OX2 6AW; UK
Classification:
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
11.8 Neuroprotection (Part of: 11 Medical treatment)
