Comparative Study of Topical Application of Timolol and Verapamil in Patients With Glaucoma Within 6 Months

Shayegan, Mohammad Reza; Boloorian, Ali Akbar; Kianoush, Sina

doi:10.1089/jop.2009.0005

Cited by 12 publications

(6 citation statements)

References 17 publications

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“…Of note, this NMDA‐model is a chemically induced RGC death model and does not induce increases in IOP. Interestingly, while chronic topical administration of verapamil can reduce IOP, systemic treatment with verapamil has little effect in lowering IOP (Liu et al ., 1996; Mikheytseva et al ., 2004; Shayegan et al ., 2009). Here, we have demonstrated the systemic neuroprotective effects of verapamil via inhibiting TXNIP expression.…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity

Al‐Gayyar

Abdelsaid

Matragoon

et al. 2011

British Journal of Pharmacology

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BACKGROUND AND PURPOSEUp-regulation of thioredoxin interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (Trx), compromises cellular antioxidant and anti-apoptotic defences and stimulates pro-inflammatory cytokines expression, implying a role for TXNIP in apoptosis. Here we have examined the causal role of TXNIP expression in mediating retinal neurotoxicity and assessed the neuroprotective actions of verapamil, a calcium channel blocker and an inhibitor of TXNIP expression. EXPERIMENTAL APPROACHRetinal neurotoxicity was induced by intravitreal injection of NMDA in Sprague-Dawley rats, which received verapamil (10 mg·kg -1 , p.o.) or vehicle. Neurotoxicity was examined by terminal dUTP nick-end labelling assay and ganglion cell count. Expression of TXNIP, apoptosis signal-regulating kinase 1 (ASK-1), NF-kB, p38 MAPK, JNK, cleaved poly-ADP-ribose polymerase (PARP), caspase-3, nitrotyrosine and 4-hydroxy-nonenal were examined by Western and slot-blot analysis. Release of TNF-a and IL-1b was examined by ELISA. KEY RESULTSNMDA injection enhanced TXNIP expression, decreased Trx activity, causing increased oxidative stress, glial activation and release of TNF-a and IL-1b. Enhanced TXNIP expression disrupted Trx/ASK-1 inhibitory complex leading to release of ASK-1 and activation of the pro-apoptotic p38 MAPK/JNK pathway, as indicated by cleaved PARP and caspase-3 expression. Treatment with verapamil blocked these effects. CONCLUSION AND IMPLICATIONSElevated TXNIP expression contributed to retinal neurotoxicity by three different mechanisms, inducing release of inflammatory mediators such as TNF-a and IL-1b, altering antioxidant status and disrupting the Trx-ASK-1 inhibitory complex leading to activation of the p38 MAPK/JNK apoptotic pathway. Targeting TXNIP expression is a potential therapeutic target for retinal neurodegenerative disease. AbbreviationsASK-1, apoptosis signal-regulating kinase 1; GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; NFL, nerve fiber layer; NMLA, N-methyl-L-aspartate; ONL, inner plexiform layer into the outer nuclear layer; PARP, poly-ADP-ribose polymerase; RGC, retinal ganglion cell; ROD, relative optical density; Trx, thioredoxin; TUNEL, terminal dUTP nick-end labelling; TXNIP, thioredoxin interacting protein BJP British Journal of Pharmacology

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Section: Discussionmentioning

confidence: 99%

Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity

Al‐Gayyar

Abdelsaid

Matragoon

et al. 2011

British Journal of Pharmacology

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“…Calcium channel blockers may also inhibit the synthesis of extracellular matrix collagen protein, suggesting beneficial effect in glaucoma. 13 CCBs cause relaxation of trabecular mesh work cells by inhibition of L-type channels which increases outfow facility of aqueous humor. The perfusion studies in dissected human eyes showed dose-related increase in outfow facility after verapamil administration.…”

Section: Introductionmentioning

confidence: 99%

Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma

Ganekal¹,

Dorairaj²,

Jhanji³

et al. 2014

Journal of Current Glaucoma Practice

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Purpose: To evaluate the effect of 0.125% verapamil and 0.5% diltiazem eye drops on intraocular pressure (IOP) in steroid-induced glaucoma in rabbit eyes.Methods: A total of 18 rabbits with steroid-induced glaucoma were divided into three groups (A, B and C; n = 6 each). Right eyes in groups A, B and C received 0.5% diltiazem, 0.125% verapamil and 0.5% timolol eye drops twice daily for 12 days, respectively; whereas, left eyes received distilled water. IOP was measured with Tono-pen XL at baseline, day 4, day 8, and day 12 of treatment.Results: Both 0.5% diltiazem and 0.125% verapamil eye drops significantly reduced IOP compared to control eyes (p < 0.05). Reduction of IOP by 0.5% diltiazem, 0.125% verapamil eye drops were comparable to 0.5% timolol. No surface toxicity or systemic side effects were noted during the study period.Conclusion: Calcium channel blockers, verapamil, and diltia-zem significantly reduced IOP in rabbiteyes. This group of drugs may have a potential role in treatment of glaucomaHow to cite this article: Ganekal S, Dorairaj S, Jhanji V, Kudlu K. Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma. J Current Glau Prac 2014;8(1):15-19.

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“…[30][31][32] In this proof of principle study, we did not intend to determine the amount of microbeads required to achieve, for example, a reduction of IOP by 5 mmHg since the pharmacokinetics of timolol differ between humans and rabbits. Indeed, previous studies have demonstrated that timolol is less effective in rabbits than humans, [33][34][35][36][37] suggesting that the use of timolol spheres may have a more marked effect in humans, and particularly in eyes with elevated IOP. Our data do demonstrate that sustained delivery of timolol is possible using this vehicle.…”

Section: Discussionmentioning

confidence: 99%

Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection

Lavik

Kuehn

Shoffstall

et al. 2016

Journal of Ocular Pharmacology and Therapeutics

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Comparative Study of Topical Application of Timolol and Verapamil in Patients With Glaucoma Within 6 Months

Abstract: It seems that topical verapamil has a similar effect to timolol in patients with open-angle glaucoma, so it can be considered as a lowering intraocular pressure agent in glaucoma patients.

Cited by 12 publications

References 17 publications

Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity

Thioredoxin interacting protein is a novel mediator of retinal inflammation and neurotoxicity

Effect of Topical Calcium Channel Blockers on Intraocular Pressure in Steroid-induced Glaucoma

Sustained Delivery of Timolol Maleate for Over 90 Days by Subconjunctival Injection

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