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N N Osborne

Publications and source records attributed to N N Osborne.

At least 19 recordsLinked to original sources
PubMed2006

Oxidative-induced retinal degeneration is attenuated by epigallocatechin gallate.

The aim of this investigation was to determine whether an ingredient of green tea, epigallocatechin gallate (EGCG) could attenuate oxidative stress-induced degeneration of the retina as occurs in age-related macular degeneration (AMD) and glaucoma. Initial in vitro studies on brain membranes showed that EGCG was approximately 10 times more potent than trolox (vitamin E analogue) at attenuating lipid peroxidation caused by the nitric oxide donor, sodium nitroprusside (SNP). Subsequent immunohistochemical studies revealed that following an intraocular injection of SNP retinal photoreceptors are affected. This was supported by electroretinogram (ERG) recordings which showed both the a- and b-wave amplitudes to be significantly reduced. RT-PCR and Western blotting techniques showed that SNP caused a significant decrease in photoreceptor-specific markers (RET-P1, rhodopsin kinase), an increase in the cell death marker caspase-3, and no change in the ganglion cell specific markers, neurofilament (NF-L) and Thy-1. Importantly, when EGCG was co-injected, the detrimental effects to the retina caused by SNP were significantly blunted. The conclusion reached from this study is that EGCG is a powerful antioxidant and when injected into the eye with SNP attenuated the detrimental influence of SNP to retinal photoreceptors. Since oxidative stress has been implicated in retinal diseases like AMD and glaucoma this study provides "proof of principle" for the idea that daily intake of EGCG may help individuals suffering from retinal diseases where oxidative stress is implicated.

Animals↗
PubMed2006

A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies.

The authors propose that light entering the eye interacts with retinal ganglion cell (RGC) axon mitochondria to generate reactive oxygen intermediates (ROI) and that when these neurons are in an energetically low state, their capacity to remove these damaging molecules is exceeded and their survival is compromised. They suggest that in the initial stages of glaucoma, RGCs exist at a low energy level because of a reduced blood flow at the optic nerve head and that in the mitochondrial optic neuropathies (MONs), this results from a primary, genetic defect in aerobic metabolism. In these states RGCs function at a reduced energy level and incident light on the retina becomes a risk factor. Preliminary laboratory studies support this proposition. Firstly, the authors have shown that light is detrimental to isolated mitochondria in an intensity dependent manner. Secondly, light triggers apoptosis of cultured, transformed RGCs and this effect is exacerbated when the cells are nutritionally deprived. Detailed studies are under way to strengthen the proposed theory. On the basis of this proposal, the authors suggest that patients with optic neuropathies such as glaucoma or at risk of developing a MON may benefit from the use of spectral filters and reducing the intensity of light entering the eye.

Apoptosis↗
PubMed2005

Neuronal death in primary retinal cultures is related to nitric oxide production, and is inhibited by erythropoietin in a glucose-sensitive manner.

The aim of this work was to investigate the interrelated effects of glucose, nitric oxide (NO) and erythropoietin on neuronal survival in retinal cultures, thereby exploring the mechanism of neuronal death in the diabetic retina. Rat retinal cells were cultured in low (5 mM) or high (15 mM) glucose concentrations. After 9 days, cell viability was assessed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and NO production was determined by the Griess reaction. Immunohistochemistry was used to quantify GABA-labelled neurones and cells staining for DNA breakdown. High or low glucose concentrations had no effect on basal NO production or the survival of neurones in culture, but treatment with N-nitro-L-arginine methyl ester reduced extracellular levels of NO and increased neuronal survival at both concentrations of glucose. Erythropoietin decreased cell death and NO levels, but only in cultures grown in low concentrations of glucose. It is concluded that erythropoietin's neurotrophic function in the retina is attenuated at glucose concentrations similar to those which occur in diabetes.

Animals↗
PubMed2004

Effectiveness of levobetaxolol and timolol at blunting retinal ischaemia is related to their calcium and sodium blocking activities: relevance to glaucoma.

Glaucoma is a chronic optic neuropathy in which retinal ganglion cells die over a number of years. The initiation of the disease and its progression may involve an ischaemic-like insult to the ganglion cell axons caused by an alteration in the quality of blood flow. Thus, to effectively treat glaucoma it may be necessary to counteract the ischaemic-like insult to the region of the optic nerve head. Studies on the isolated optic nerve suggest that substances that reduce the influx of sodium would be particularly effective neuroprotectants. Significantly, of the presently used antiglaucoma substances, only beta-blockers can reduce sodium influx into cells. Moreover, they also reduce the influx of calcium and this would be expected to benefit the survival of insulted neurones. Betaxolol is the most effective antiglaucoma drug at reducing sodium/calcium influx. Our electroretinographic data indicated that topical application of levobetaxolol to rats attenuated the effects of ischaemia/reperfusion injury. Timolol was also effective but to a lesser extent. Based on these data we conclude that beta-blockers may be able to blunt ganglion cell death in glaucoma, and that levobetaxolol may be a more effective neuroprotectant than timolol because of its greater capacity to block sodium and calcium influx.

Animals↗
PubMed2004

[Neuroprotection against glaucoma remains a concept].

According to estimates made by WHO, approximately 105 million people are affected worldwide by glaucoma. This can be defined as progressive optic neuropathy with structural damage of the optic nerve head and death of retinal ganglion cells. Although elevated IOP is considered responsible for glaucoma, lowering the pressure often does not result in improvement. For this reason, other etiological factors are presumed, which are presented in the following contribution. The role of neuroprotective agents in the treatment of glaucoma is discussed. The pattern of ganglion cell death specific to glaucoma seems to suggest that certain ganglion cells could be more sensitive than others. The theory of "cumulative damage" in this case includes the hypothesis that the delayed onset of many neurodegenerative diseases such as glaucoma, Alzheimer's disease, or Parkinson's disease can be attributed to the age-related accumulation of toxic substances in the ganglion cells. On the contrary, the theory of "singular damage" is based on the assumption that certain ganglion cells are in a state of reduced homeostasis caused by the expression of so-called mutant response genes. Therapeutic approaches worthy of consideration based on their side effect profile and efficacy in animal trials, are presented.

Animals↗
PubMed2004

[Ischemia and hypoxia. An attempt to explain the different rates of retinal ganglion cell death in glaucoma].

In hypoxic or ischemic states, the receptors of the ganglion cells are overstimulated by release of neurotransmitters. Glutamate and GABA (gamma-aminobutyric acid) are the decisive neurotransmitters in the retina. It is presumed that the extent of cell death depends on the degree of depolarization, which in turn is determined by the amount of excitatory (glutamate) or inhibitory (GABA) receptors of the corresponding ganglion cell. The assumption is that the receptor profile of the individual ganglion cells determines the sensitivity of these cells to hypoxia or ischemia, i.e., the time up to cell death, and thus represents the underlying cause of the different rates of cell death in primary chronic open-angle glaucoma. Research on this receptor profile could be of pivotal importance for the approach to neuroprotective treatment of primary chronic open-angle glaucoma.

Animals↗
PubMed2004

Methamphetamine exacerbates the toxic effect of kainic acid in the adult rat retina.

The recreational use of the psychoactive drug, methamphetamine has increased markedly over the last three decades. It has long been known that this drug has detrimental effects upon the mammalian brain monoaminergic system, but the long- or short-term effects on the retina, a neurological extension of the central nervous system, have received little attention. The aim of this study was, therefore, to determine whether intraocular injection of methamphetamine (MA) is toxic to the healthy adult rat retina and to analyse its effects on the compromised retina after an injection of the ionotropic glutamate receptor agonist, kainate, which is known to cause retinal neuropathology. The equivalent of 1 mM (in the vitreous humour) MA and/or kainate (40 microM) were injected intravitreally. Flash electroretinograms (ERGs) were recorded before and 2 and 4 days after treatment. Five days after treatment, animals were killed and the retinas analysed either for the immunohistochemical localisation of various antigens or for electrophoresis/Western blotting. Some animals were kept for 19 days after treatment and the retinas analysed for tyrosine hydroxylase immunoreactivity. No differences could be found between vehicle- and MA-treated retinas with respect to the nature or localisation of either tyrosine hydroxylase immunoreactivity after 5 or 19 days or other antigens after 5 days. Moreover, the normal ERG and GFAP and calretinin protein antigens were unaffected by MA. Kainate treatment, however, caused a change in the ERGs after 2 and 4 days, an alteration in every antigen localised by immunohistochemistry and an increase in the retinal levels of calretinin and GFAP proteins. Significantly, the changes seen in the b-wave amplitude and implicit time of the ERG after 4 days and the increased level of GFAP protein after 5 days following kainate treatment were enhanced when MA was co-injected. Intravitreal injection of methamphetamine had no detectable detrimental effect on the normal adult rat retina but exacerbated the damaging effects of kainic acid. Such data suggest that a neurotoxic effect of MA may be more obviously illustrated when the tissue is already compromised as occurs in, for example, ischemia.

Animals↗
PubMed2004

Optic nerve and neuroprotection strategies.

BACKGROUND: Experimental studies have yielded a wealth of information related to the mechanism of ganglion cell death following injury either to the myelinated ganglion cell axon or to the ganglion cell body. However, no suitable animal models exist where injury can be directed to the optic nerve head region, particularly the unmyelinated ganglion cell axons. The process of relating the data from the various animal models to many different types of optic neuropathies in man must, therefore, be cautious. RESULTS: Extensive studies on the isolated optic nerve have yielded valuable information on the way white matter is affected by ischaemia and how certain types of compounds can attenuate the process. Moreover, there are now persuasive data on how ganglion cell survival is affected when the ocular blood flow is reduced in various animal models. As a consequence, the molecular mechanisms involved in ganglion cell death are fairly well understood and various pharmacological agents have been shown to blunt the process when delivered before or shortly after the insult. CONCLUSIONS: A battery of agents now exist that can blunt animal ganglion cell death irrespective of whether the insult was to the ganglion cell body or the myelinated axon. Whether this information can be applied for use in patients remains a matter of debate, and major obstacles need to be overcome before the laboratory studies may be applied clinically. These include the delivery of the pharmacological agents to the site of ganglion cell injury and side effects to the patients. Moreover, it is necessary to establish whether effective neuroprotection is only possible when the drug is administered at a defined time after injury to the ganglion cells. This information is essential in order to pursue the idea that a neuroprotective strategy can be applied to a disease like glaucoma, where ganglion cell death appears to occur at different times during the lifetime of the patient.

Animals↗
PubMed2004

Hypoglycaemia exacerbates ischaemic retinal injury in rats.

AIMS: To determine the effect of hypoglycaemia on ischaemic retinal injury. METHODS: Rat retinal cultures were incubated in varying concentrations of glucose while placed under standardised anoxic conditions, and the number of surviving GABA immunoreactive neurons was assessed using immunocytochemistry. Hypoglycaemia was induced in age and sex matched Wistar rats by an injection of rapid acting insulin. The blood, vitreous, and retinal glucose concentrations were measured using a hexokinase assay kit. Electroretinography, semiquantitative RT-PCR, and histology were used to compare the functional and structural retinal injury in these rats with the injury in appropriate controls after a period of pressure induced retinal ischaemia. RESULTS: Retinal cultures maintained in low glucose concentrations (<1 mM) had fewer surviving GABA immunoreactive neurons after an anoxic insult compared with retinal cultures maintained in 5 mM glucose. Hypoglycaemic rats had significantly lower vitreous glucose concentrations (0.57 (SEM 0.04) mM) than the control rats (3.1 (0.70) mM; p<0.001). The a-wave and b-wave amplitudes of the hypoglycaemic rats after 3 and 7 days of reperfusion were significantly lower than the amplitudes of the control rats. Furthermore, the level of Thy-1 mRNA (a retinal ganglion cell marker) was significantly lower in the hypoglycaemic group (p<0.001) and there was a corresponding exacerbation of structural injury compared with the controls. CONCLUSION: Hypoglycaemia causes a significant reduction in vitreous glucose levels and exacerbates ischaemic retinal injury.

Acute Disease↗
PubMed2003

The beta-adrenoceptor antagonists metipranolol and timolol are retinal neuroprotectants: comparison with betaxolol.

beta-adrenoceptor antagonists are used clinically to reduce elevated intraocular pressure in glaucoma which is characterised by a loss of retinal ganglion cells. Previous studies have shown that the beta(1)-selective adrenoceptor antagonist, betaxolol, is additionally able to protect retinal neurones in vitro and ganglion cells in vivo from the detrimental effects of either ischemia-reperfusion or from excitotoxicity, after topical application. The neuroprotective effect of betaxolol is thought not to be elicited through an interaction with beta-adrenoceptors, but by its ability to reduce influx of sodium and calcium through voltage-sensitive calcium and sodium channels. In the present study it is shown that the non-selective beta-adrenoceptor antagonists, metipranolol and timolol behave like betaxolol. When topically applied they all attenuate the detrimental effect of ischemia-reperfusion. Protection of the retina was determined by evaluating changes in the electroretinogram and by assessing the loss of mRNA for Thy-1, which is expressed in retinal ganglion cells. In addition, studies conducted on neurones in mixed retinal cultures demonstrated that metipranolol, betaxolol and timolol were all able to partially counteract anoxia-induced cell loss and viability reduction. The influence of timolol was, however, not significant. Within the confines of these investigations, an order of neuroprotective efficacy was delineated for the three beta-adrenoceptor antagonists: betaxolol>metipranolol>timolol. The ability of the beta-adrenoceptor antagonists to attenuate ligand-induced stimulation of calcium and sodium entry into neuronal preparations showed a similar order of effectiveness. In conclusion, the ability to confer neuroprotection to retinal neurones is a common feature of three ophthalmic beta-adrenoceptor antagonists (betaxolol, metipranolol and timolol). A comparison of the effectiveness of the individual compounds in protecting retinal cells in vivo was not possible in these studies. However, in vitro studies show that the capacity of the individual beta-adrenoceptor antagonists to act as neuroprotectants appears to relate to their capacity to attenuate neuronal calcium and sodium influx.

Adrenergic beta-Antagonists↗
PubMed2003

Effects of intraocular injection of a low concentration of zinc on the rat retina.

The main aim of this study was to investigate whether intraocular injection of low concentrations of zinc (no greater than 10 microM) aid the survival of ganglion cells in the rat retina after excitotoxic (NMDA) and ischemia/reperfusion injuries. We also determined whether low amounts of zinc cause any detectable retinal toxicity. Intraocular injection of NMDA caused substantial reductions in the mRNA levels of the ganglion cell-specific markers Thy-1 and neurofilament light (NF-L). Co-injection of 0.1 or 1 nmol zinc neither diminished nor exacerbated the effect of NMDA on the levels of these mRNAs. Likewise, ischemia/reperfusion caused significant decreases in the levels of Thy-1 and NF-L mRNAs and in the b-wave amplitude of the electroretinogram. These effects were not counteracted by injection of zinc. Intraocular injection of NMDA caused marked toxicological effects in retinal glial cells, including upregulations of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glial fibrial acidic protein (GFAP), basic fibroblast growth factor (FGF-2) and ciliary neurotrophic factor (CNTF). Interestingly, injection of 1 nmol zinc caused no changes in the levels of COX-2 and iNOS, yet produced similar, although quantitatively less pronounced, changes in FGF-2, GFAP and CNTF. The upregulations of FGF-2 and CNTF suggest that increasing zinc intake may benefit injured retinal neurons. However, this was not found to be the case in the present studies, perhaps due to the acute nature of the injury paradigms utilised.

Animals↗
PubMed2003

Some current ideas on the pathogenesis and the role of neuroprotection in glaucomatous optic neuropathy.

The primary features of glaucomatous optic neuropathy are characteristic changes in the optic nerve head, a decrease in number of surviving ganglion cells and a reduction in vision. It is now generally accepted that a number of factors, including elevated intraocular pressure, could lead to the changes seen in the optic nerve head and to obtain a pharmacological means to treat the causes will vary from patient to patient. In contrast, a cascade of events have been proposed to explain how the changes in the optic nerve head may lead to the slow and differential death of ganglion cells in the disease. It is also proposed that drugs (neuroprotectants) influencing this cascade of events can attenuate ganglion cell death and lead to the treatment of all glaucoma patients.

Animals↗
PubMed2002

Alpha-lipoic acid protects the retina against ischemia-reperfusion.

The aim of this study was to examine whether the antioxidant alpha-lipoic acid protects retinal neurons from ischemia-reperfusion injury. Rats were injected intraperitoneally with either vehicle or alpha-lipoic acid (100 mg/kg) once daily for 11 days. On the third day, ischemia was delivered to the rat retina by raising the intraocular pressure above systolic blood pressure for 45 min. The electroretinogram was measured prior to ischemia and 5 days after reperfusion. Rats were killed 5 or 8 days after reperfusion and the retinas were processed for immunohistochemistry and for determination of mRNA levels by RT-PCR. Ischemia-reperfusion caused a significant reduction of the a- and b-wave amplitudes of the electroretinogram, a decrease in nitric oxide synthase and Thy-1 immunoreactivities, a decrease of retinal ganglion cell-specific mRNAs and an increase in bFGF and CNTF mRNA levels. All of these changes were clearly counteracted by alpha-lipoic acid. Moreover, in mixed rat retinal cultures, alpha-lipoic acid partially counteracted the loss of GABA-immunoreactive neurons induced by anoxia. The results of the study demonstrate that alpha-lipoic acid provides protection to the retina as a whole, and to ganglion cells in particular, from ischemia-reperfusion injuries. alpha-Lipoic acid also displayed negligible affinity for voltage-dependent sodium and calcium channels.

Anesthetics, Local↗
PubMed2001

Topically applied clonidine protects the rat retina from ischaemia/reperfusion by stimulating alpha(2)-adrenoceptors and not by an action on imidazoline receptors.

Ischaemia was induced to the rat retina by raising the intraocular pressure above the systolic blood pressure for 45 min. After a reperfusion period of 5 days, alterations in the localisation of choline acetyltransferase (ChAT) and calretinin immunoreactivities, a reduction in the thickness of the inner retinal layers and a decline in the b-wave amplitude of the electroretinogram were recorded. These changes were blunted when clonidine was injected intraperitoneally before or after ischaemia or when applied topically by a specific regime. Other alpha(2)-adrenoceptor agonists, brimonidine and apraclonidine, acted in a similar way to clonidine when applied topically but because of the number of experiments carried out a comparison between the effectiveness of the different alpha(2)-adrenoceptor agonists was not possible. The protective effect of clonidine was attenuated when the alpha(2)-adrenoceptor antagonists yohimbine or rauwolscine were co-administered, suggesting that the mechanism of action of the drug is to stimulate alpha(2)-adrenoceptors. In addition, the imidazoline receptor ligands, BU-226 and AGN-192403 did not blunt the effect of ischaemia/reperfusion, supporting the notion that the protective action of the alpha(2)-adrenoceptor agonists does not involve imidazoline sites but rather the activation of alpha(2)-adrenoceptors. The protective effect of 0.5% clonidine appeared to be greater when topically applied to the eye that received ischaemia than when applied by the same regime to the contralateral eye. These studies suggest that while most of topically applied clonidine reaches the retina by a systemic route one cannot rule out additional pathways.

Adrenergic alpha-Agonists↗
PubMed2001

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.

Adrenergic beta-Antagonists↗
PubMed2001

Voltage-dependent calcium channels in the rat retina: involvement in NMDA-stimulated influx of calcium.

Rises in intracellular Ca2+ induced by activation of glutamate receptors are of ultimate importance for neuronal excitability and pathophysiological processes. In the present study, we aimed to elucidate the types of voltage-dependent Ca2+ channels involved in the NMDA-stimulated influx of Ca2+ into the isolated rat retina by using selective blockers. Additionally, the number of binding sites for radioligands labelling L- ([3H]nitrendipine), N- ([125I]omega-conotoxin MVIIA) and P/Q-type ([125I]omega-conotoxin MVIIC) Ca2+ channels was assessed in the rat retina and, for further comparison, in the rat cortex. Incubation of isolated rat retinas with 100 microM NMDA produced a three-fold increase in the influx of 45Ca2+ that was completely blunted by MK-801, a NMDA receptor antagonist, and partially attenuated (approximately 20%) by tetrodotoxin, a Na+ channel blocker. The L-type Ca2+ channel blocker nifedipine reduced NMDA-stimulated Ca2+ influx in a dose-related fashion, with a maximum reduction of approximately 50%. Similar effects were observed with verapamil and diltiazem. Blockers of N- and P/Q-type Ca2+ channels had no significant effect on the influx of Ca2+ evoked by NMDA. Co2+, a non-specific Ca2+ channel blocker, caused an inhibition of NMDA-stimulated Ca2+ influx similar to that of nifedipine. Therefore, of all voltage-dependent Ca2+ channels, L-type channels appear to make the greatest contribution (up to 50%) to the NMDA-stimulated influx of Ca2+ into the isolated rat retina. This finding contrasts with evidence obtained in brain neurones supporting a role for L-, N- and P/Q-type channels in NMDA-evoked Ca2+ signals. A comparison of the number of radioligand binding sites associated with L-, N- or P/Q-type Ca2+ channels in the rat cortex and retina revealed that such a difference cannot be ascribed to a distinct expression pattern of these channels in both tissues, although some variations were found. Interestingly, a different affinity of [3H]nitrendipine for L-type Ca2+ channels in the rat retina and cortex was observed which may reflect the expression of different classes of L-type channels in these tissues. The ability of L-type Ca2+ channel blockers to attenuate NMDA-stimulated Ca2+ influx may underlie their neuroprotective effects in the retina.

Analysis of Variance↗
PubMed2001

Comparative effects of antiglaucoma drugs on voltage-dependent calcium channels.

BACKGROUND: Experimental evidence suggests that substances able to interact with voltage-dependent Ca2+ channels (VDCCs) might be beneficial in glaucoma management. It was therefore of significance to show that beta-adrenoceptor antagonists used in glaucoma directly interact with L-type VDCCs. In the present study, the affinity of several antiglaucoma drugs (betaxolol, carteolol, levobunolol, timolol, brimonidine, dorzolamide, latanoprost and pilocarpine) for these and other VDCCs was investigated using radioligand binding assays. Experiments were also carried out to assess the effect of antiglaucoma drugs on the NMDA-stimulated Ca2+ influx into isolated rat retinas. METHODS: Competition radioligand binding studies to L-, N- and P/Q-type VDCCs were performed in rat cortical homogenates. The effects of antiglaucoma drugs on the NMDA-stimulated influx of 45Ca2+ were studied in isolated rat retinas. RESULTS: Only beta-adrenoceptor antagonists significantly interacted with radioligand binding to L-type VDCCs, with betaxolol displaying the highest potency. None of the antiglaucoma drugs tested showed any significant affinity for either N- or P/Q-type VDCCs. Only beta-adrenoceptor antagonists attenuated the NMDA-stimulated 45Ca2+ influx into isolated rat retinas, with betaxolol exhibiting at least 10 times higher potency than timolol. Brimonidine, dorzolamide, latanoprost and pilocarpine did not elicit any significant effect on the NMDA-stimulated 45Ca2+ influx. Additional experiments strongly suggested that the effect of betaxolol on the NMDA-stimulated 45Ca2+ resulted from inhibition of L-type VDCCs. CONCLUSION: Of the antiglaucoma drugs investigated, betaxolol displays the greatest L-type VDCC-blocking activity and this may be of clinical relevance. Such a characteristic could account for some of its described ocular actions.

Adrenergic beta-Antagonists↗