Protective effects of betaxolol in eyes with kainic acid-induced neuronal death.
ABSTRACT In the present study, we investigated whether betaxolol, a selective beta1-adrenoceptor antagonist, has neuroprotective effect on kainic acid (KA)-induced retinal damage. Neurotoxicities were induced in adult male rats by intravitreal injection of KA (total amount, 6 nmol). To examine the neuroprotective effects of betaxolol, rats were pretreated with betaxolol topically 60 min before KA injection to the rat eyes and twice daily for 1, 3, and 7 days after KA injection. The neuroprotective effects of betaxolol were estimated by measuring the thickness of the various retinal layers, and by counting the number of choline acetyltransferase (ChAT)- and tyrosine hydroxylase (TH)-positive cells in each retinal layer. The retina is highly vulnerable to KA-induced neuronal damage. Morphometric analysis of retinal damage in KA injected eyes, the thickness of the retinal layers decreased markedly after KA injection period of both 3 and 7 days. Furthermore, the numbers of ChAT- and TH-positive cells were significantly reduced by intravitreal injection of KA. However, when two drops of betaxolol, once before KA injection and twice daily for 7 days after KA injection, were continuously administered, the reductions in the retinal thickness and the retinal ChAT- and TH-positive cells were significantly attenuated. The present study suggests that topically applied betaxolol has neuroprotective effect on the retinal cell damage due to KA-induced neurotoxicity.
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ABSTRACT: Kainate receptors mediate fast, excitatory synaptic transmission for a range of inner neurons in the mammalian retina. However, allocation of functional kainate receptors to known cell types and their sensitivity remains unresolved. Using the cation channel probe 1-amino-4-guanidobutane agmatine (AGB), we investigated kainate sensitivity of neurochemically identified cell populations within the structurally intact rat retina. Most inner retinal neuron populations responded to kainate in a concentration dependent manner. OFF cone bipolar cells demonstrated the highest sensitivity of all inner neurons to kainate. Immunocytochemical localization of AGB and macromolecular markers confirmed Type 2 BCs as part of this kainate sensitive population. The majority of amacrine (ACs) and ganglion cells (GCs) showed kainate responses with different sensitivities between major neurochemical classes (GABA/Glycine ACs > Glycine ACs > GABA ACs; Glu/weakly GABA GCs > Glu GCs). Conventional and displaced cholinergic ACs were highly responsive to kainate whilst dopaminergic ACs do not appear to express functional kainate receptors. These findings further contribute to our understanding of neuronal networks in complex multi-cellular tissues. J. Comp. Neurol., 2013. © 2013 Wiley Periodicals, Inc.The Journal of Comparative Neurology 01/2013; · 3.66 Impact Factor
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ABSTRACT: Calcium channel blockers (CCBs), which alter the intracellular calcium concentration by modifying calcium flux across cell membranes and affect various intracellular signaling processes, have been long and widely used to treat essential hypertension and certain types of cardiac diseases such as angina pectoris. Among five subtypes of calcium channels, only specific agents for L-type calcium channels have been used as therapeutics. Animal experiments have indicated that topical application of CCBs, especially verapamil, caused significant intraocular pressure (IOP) reductions, while ocular hypotensive effects in humans were not substantial. Although the results obtained for nifedipine and nimodipine were not always consistent, CCBs generally dilate isolated ocular vessels and increase ocular blood flow in experimental animals, normal humans, and patients with open-angle glaucoma (OAG). Several single-centered, hospital-based, prospective studies have suggested that nimodipine, brovincamine, and nilvadipine had beneficial effects on visual function not only in normal humans but also in patients with OAG, while the results of population-based and case-controlled studies were not always consistent with those obtained in hospital-based studies. In vitro studies showed that CCBs exerted neuroprotective effects on neurons undergoing apoptosis and necrosis. Although the neuroprotective effects of CCBs have been well documented in experimental cerebral ischemia models, no controlled studies have shown the clinical efficacy of CCBs in stroke or cerebral ischemia. Neuroprotective effects also were documented in retinal ganglion cells and photoreceptors in experimental animals. Some ophthalmic beta-adrenoceptor antagonists, especially betaxolol, interact with L-type calcium channels and show calcium channel-blocking activity, which may be partly responsible for the neuroprotective effects of these drugs reported in experimental animals. Based on the reported findings of CCBs and that the results of clinical studies in acute cerebral ischemia may not be directly applicable to a chronic neurodegenerative ocular disorder, such as OAG, CCBs deserve future study to investigate strategies that are additive or synergetic to ocular hypotensive therapy for OAG, especially in patients with lower IOP.Progress in Retinal and Eye Research 10/2010; 30(1):54-71. · 9.44 Impact Factor
Chapter: Neuroprotection in Glaucoma11/2011; , ISBN: 978-953-307-591-4