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: Several factors besides high intraocular pressure assumed to be associated with the development and progression of glaucoma, and calcium channel blockers (CCBs) have been an anticipated option for glaucoma treatment by improving ocular perfusion and/or exerting neuroprotective effects on retinal ganglion cells with safety established in wide and long-term usage. Decrease in IOP has been reported after topical application of CCBs, however, the effect is much smaller and almost negligible after systemic application. Various CCBs have been reported to increase posterior ocular blood flow in vivo and to exert direct neuroprotection in neurons in vitro. Distribution of the drug at a pharmacologically active concentration in the posterior ocular tissues across the blood-brain barrier or blood-retina barrier, especially in the optic nerve head and retina where the ganglion cells mainly suffer from glaucomatous damage, is essential for clinical treatment of glaucoma. Improved visual functions such as sensitivity in the visual field test has been reported after administration of CCBs, but evidences from the randomized studies have been limited and effects of CCBs on blood flow and direct neuroprotection is hardly distinguished from each other.European journal of pharmacology 11/2013; · 2.59 Impact Factor
Chapter: Neuroprotection in GlaucomaGlaucoma - Basic and Clinical Concepts, 11/2011; , ISBN: 978-953-307-591-4