Topically applied betaxolol attenuates ischaemia-induced effects to the rat retina and stimulates BDNF mRNA.
It has previously been reported that the beta(1)-adrenoceptor antagonist, betaxolol, can protect retinal neurones from ischaemia when applied topically. It has further been shown that betaxolol can reduce influx of both sodium or calcium into neurones through interaction at neurotoxin site 2 of the sodium channel and the L-type calcium channel, respectively. The present study sought to further investigate the neuroprotective mode of action of betaxolol in the rat retina. Rats were treated topically with L-betaxolol for 10, 5 and 1 min before ischaemia, induced by raising the intraocular pressure above systolic blood pressure for 45 min. This was followed by reperfusion of 3 or 5 days where L-betaxolol was applied topically twice daily. Ischaemia plus reperfusion caused both a loss of immunoreactivity for choline acetyl transferase (ChAT) and a marked reduction of the b-wave of the electroretinogram (ERG). Treatment, as described, with topical L-betaxolol, completely blunted the effects upon ChAT immunoreactivity and caused a significant reversal of the ERG changes. Furthermore, other rats treated topically with commercially available racemic betaxolol (Betoptic Solution, 0.5%) for 6 hr had raised levels of mRNA for brain derived neurotrophic factor (BDNF) but not for basic fibroblast growth factor (bFGF) in their retinas. The combined data provide further evidence that betaxolol can blunt the effects of ischaemia to the rat retina when applied topically just before the insult. Furthermore, the finding that retinal levels of BDNF mRNA are raised following topical betaxolol treatment shows that not only can this drug reach the retina but that it can also induce changes in expression of factors which are known, themselves, to provide neuroprotection to retinal neurones.
Wood
J P
JP
Nuffield Laboratory of Ophthalmology, Walton Street, Oxford, OX2 6AW, UK.
DeSantis
L
L
Chao
H M
HM
Osborne
N N
NN
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D015784:Betaxolol / Q000627:therapeutic use*; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D004596:Electroretinography; D007511:Ischemia / Q000188:drug therapy*; D009414:Nerve Growth Factors / Q000187:drug effects* / Q000235:genetics; D009883:Ophthalmic Solutions; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects*; D012171:Retinal Vessels / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D009414:Nerve Growth Factors; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D002795:Choline O-Acetyltransferase; D015784:Betaxolol