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

Wood, J. K.; Kg, Schmidt; Melena, José; Chidlow, Glyn; Allmeier, Helmut; Osborne, Neville N.

doi:10.1016/s0014-4835(02)00335-4

Cited by 96 publications

(52 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The neuroprotective properties of ophthalmic β-antagonists, especially betaxolol, on NMDA / glutamate-dependent signals such as intracellular Ca 2+ increase (9, 10, 25) and cell death (11,26,27) have been demonstrated in previous studies using RGCs, but it has not been well discussed whether antiglaucoma drugs exert direct antagonistic effects on NMDA-receptor function. Therefore, we firstly investigated the direct effects of different types of antiglaucoma drugs on NMDA-and non-NMDA (AMPA)-receptor function using a Xenopus oocyte expression system.…”

Section: Discussionmentioning

confidence: 99%

Direct Inhibition of N-Methyl-D-Aspartate (NMDA)-Receptor Function by Antiglaucomatous β-Antagonists

et al. 2008

View full text Add to dashboard Cite

Abstract. In the present study, we investigated the direct effects of antiglaucoma drugs (timolol, betaxolol, pilocarpine, and latanoprost) on N-methyl-D-aspartate (NMDA)-receptor function using a Xenopus oocytes expression system and electrophysiological techniques. In oocytes expressing wild-type NMDA (NR1a / NR2A) receptors, timolol and betaxolol significantly inhibited glutamate-evoked currents, whereas less inhibition was obtained with pilocarpine, and latanoprost had few effects. Moreover, the effect of timolol and betaxolol was noncompetitive with respect to glutamate. Mutations that changed Asn616 of the NR1a subunit, a critical residue for Mg 2+ blocking of NMDA receptors, to Arg (N616R) or Gln (N616Q) almost eliminated the inhibitory effects of timolol and betaxolol, as well as the blocking effect of Mg 2+. Experiments were also carried out to examine the protective effects of timolol and betaxolol against death of oocytes expressing NMDA receptors. During incubation of oocytes, especially in Mg 2+ -free medium, cell death was induced by addition of glutamate because of the continuous activation of the NMDA receptors expressed. Timolol and betaxolol significantly improved oocyte viability when they were added during the incubation period. These results suggest that timolol and betaxolol may have an additional role that they directly inhibit NMDA-receptor function, possibly via N616 of the NR1a subunit.

show abstract

Section: Discussionmentioning

confidence: 99%

Direct Inhibition of N-Methyl-D-Aspartate (NMDA)-Receptor Function by Antiglaucomatous β-Antagonists

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Although these drugs have been largely replaced as first line therapy by prostaglandin analogs, they are still used in many cases. Timolol and metipranolol have been claimed to be neuroprotective (Wood et al, 2003).…”

Section: Medical Treatment Of Glaucomamentioning

confidence: 99%

Mechanism of Aqueous Humor Secretion, Its Regulation and Relevance to Glaucoma

Shahidullah¹,

Almalki²,

Delamere³

2011

Glaucoma - Basic and Clinical Concepts

View full text Add to dashboard Cite

“…During reperfusion, a limited recovery of the a-and b-waves of the electroretinogram occurs depending on the magnitude and time of the previously raised IOP. [54][55][56] Importantly, it is the inner retina, and particularly the ganglion cells, that are affected in these animals, and as a consequence, much has been learnt about the mechanisms of ganglion cell death and the types of substances that are able to attenuate the death process (Table 3).…”

Section: Studies On the Isolated Anoxic Optic Nerve And Possible Thermentioning

confidence: 99%

Optic nerve and neuroprotection strategies

Osborne

Chidlow

Layton

et al. 2004

Eye

Self Cite

View full text Add to dashboard Cite

Background Experimental studies have yielded a wealth of information related to the mechanism of ganglion cell death following injury either to the mylinated 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 unmylinated 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 mylinated 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

show abstract

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

Cited by 96 publications

References 61 publications

Direct Inhibition of N-Methyl-D-Aspartate (NMDA)-Receptor Function by Antiglaucomatous β-Antagonists

Direct Inhibition of N-Methyl-D-Aspartate (NMDA)-Receptor Function by Antiglaucomatous β-Antagonists

Mechanism of Aqueous Humor Secretion, Its Regulation and Relevance to Glaucoma

Optic nerve and neuroprotection strategies

Contact Info

Product

Resources

About