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

Ganekal, Sunil; Dorairaj, Syril; Jhanji, Vishal; Kudlu, Krishnaprasad

doi:10.5005/jp-journals-10008-1155

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…Rabbit's experimental studies reported the hypotensive effect of a single topical administration dose of flunarizine after 1 h [33]. Our findings are consistent with Ashutosh et al [34] and Irina et al [35] reported a preventable effect of CCBs on glucose-and adrenaline-induced acute glaucoma in rabbits. In addition, the previous studies show that levamlodipine has a good impact on decreasing IOP in rabbits' chronic glaucoma models [15].…”

Section: Discussionsupporting

confidence: 91%

The Effect of Levamlodipine in Glucose-Induced Acute Model of Glaucoma in Rabbits

Abdulsahib¹

2021

Open Access Maced J Med Sci

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BACKGROUND: Loss of vision and irreversible blindness are the main consequences of glaucoma. There are two main types of glaucoma: Chronic and acute. AIM: This work aimed to evaluate the intraocular effect of levamlodipine on the acute model of glaucoma in rabbits. METHODS: Eighteen white albino rabbits of both sexes weighing about 2 kg. We divided them into three groups (six animals in each group) used in the experiment. We use the right eye to evaluate the effect of the test drug and used the left eye as a control (vehicle only). We used the first group to evaluate levamlodipine (0.25%), the second group to estimate levamlodipine (0.5%), and the third group to assess pilocarpine 2% (positive control). Drugs were administered 30 min before induction. RESULTS: Glucose (5%) fluid produces a significant intraocular pressure (IOP) elevation after 30 min of administration in the left eye (p ˂ 0.001). Pre-treatment topical administration of levamlodipine (0.25%) prevents the rise in the IOP significantly (p ˂ 0.001) in the right eye when compared to the control group (left eye). Moreover, compared with the eyes of the control group at all stages of the experiment, the topical administration of levamlodipine (0.5%) has a significant preventable effect (p ˂ 0.001), compared with the control group. The IOP of the local pilocarpine (2%) in the third group was significantly decreased (p ˂ 0.001). Finally, compared with levamlodipine (0.5%), pilocarpine has a more significant effect in preventing a rapid increase in intraocular pressure (p ˂ 0.001). CONCLUSION: Levamlodipine is a promising therapeutic agent for patients vulnerable to acute glaucoma.

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Section: Discussionsupporting

confidence: 91%

The Effect of Levamlodipine in Glucose-Induced Acute Model of Glaucoma in Rabbits

Abdulsahib¹

2021

Open Access Maced J Med Sci

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“…Previous studies have demonstrated a link between Ca 2+ , calcium channels and glaucoma 44 – 53 , providing a historical backdrop for our discovery of the role of Cacna2d1 in IOP modulation. Because Ca 2+ likely plays a role in the pathophysiology of glaucoma 45 , systemic calcium channel blockers (CCBs) (e.g., verapamil, diltiazem, or nimodipine) have been evaluated as plausible therapies for POAG.…”

Section: Discussionmentioning

confidence: 98%

“…Because Ca 2+ likely plays a role in the pathophysiology of glaucoma 45 , systemic calcium channel blockers (CCBs) (e.g., verapamil, diltiazem, or nimodipine) have been evaluated as plausible therapies for POAG. However, the outcomes of these investigations have been inconsistent, with some studies demonstrating that CCBs are effective in lowering IOP, protecting ganglion cells, increasing ocular blood flow and improving visual function while others fail to replicate those results 46 – 53 . In all studies performed to date, however, CCBs have targeted the α1 pore of the Ca 2+ channel and have used a systemic route of administration.…”

Section: Discussionmentioning

confidence: 99%

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

et al. 2017

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Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.

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“…These may thereby produce disease-causing signals and contribute to severe pathologies as those observed in heart failure, muscular dystrophy, diabetes, or neurodegenerative diseases [10, 11]. Also, considering the potential role of calcium channel blockers in treatment of glaucoma [12], RYR2 may be a potential candidate in POAG.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case–control study

et al. 2019

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Objective: The genetic spectrum of primary open-angle glaucoma (POAG) in middle-eastern Saudi's is still elusive. To this end, we investigated an association between rs693421, rs2499601 and their haplotypes at chromosome 1q43 locus with POAG and its related clinical phenotypes. Genotyping was performed with TaqMan ® assays. Haplotypes and their interaction analysis were carried out by SHEsis and SNPStats online tools. Results: The minor "T" allele frequency of rs693421 was 0.48 in controls and 0.52 in cases (odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.54, p = 0.368). Similarly, for rs2499601, the minor "C" allele frequency was 0.49 in controls as compared to 0.53 in cases (OR = 1.19, 95% CI 0.89-1.60, p = 0.236). Besides, genotype distribution for both these polymorphisms was also not significant in additive, dominant and recessive models. rs693421 and rs2499601, showed significant linkage disequilibrium (D' statistics = 0.69, p < 0.001) but haplotype association was non-significant (p = 0.698). The significance did not vary after adjustment to age and sex. No significant genotype association was observed with intraocular pressure, cup/disc ratio and number of anti-glaucoma medication in POAG group. Furthermore, age, sex and genotypes did not contribute any significant risk of POAG in regression analysis. We report no association between rs693421, rs2499601 and their haplotypes with POAG and related phenotypes.

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

Cited by 10 publications

References 29 publications

The Effect of Levamlodipine in Glucose-Induced Acute Model of Glaucoma in Rabbits

The Effect of Levamlodipine in Glucose-Induced Acute Model of Glaucoma in Rabbits

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Polymorphisms rs693421 and rs2499601 at locus 1q43 and their haplotypes are not associated with primary open-angle glaucoma: a case–control study

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