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Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency

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Loma Lozano, Patricia and Guzmán Aránguez, Ana Isabel and Pérez de Lara, María Jesús and Pintor, Jesús (2015) Diadenosine tetraphosphate improves adrenergic anti-glaucomatous drug delivery and efficiency. Experimental Eye Research, 134 (1). pp. 141-147. ISSN 0014-4835

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Official URL: http://dx.doi.org/10.1016/j.exer.2015.02.014



Abstract

The effect of the dinucleotide P1, P4-Di (adenosine-5') tetraphosphate (Ap4A) in improving adrenergic anti-glaucomatous delivery by modifying the tight junction proteins of the corneal epithelium was evaluated. Stratified human corneal epithelial cells (HCLE) were treated with Ap4A (100μM) for 5min and TJ protein levels and barrier function were analysed by western blotting and transepithelial electrical resistance (TEER), respectively. Western blot experiments showed a significantreduction at 2h (45% reduction of ZO-1 and 65% reduction of occludin protein levels) as compared to non-treated (control) cells. Two hours after Ap4A treatment, TEER values were significantly reduced (65% as compared to control levels (p<0.001)), indicating an increase in corneal barrier permeability. Topical application of Ap4A in New Zealand white rabbits two hours before the instillation of the hypotensor compounds (the α2-adrenergic receptor agonist, brimonidine and the β-adrenergic receptor antagonist, timolol), improved the delivery of these compounds to the anterior chamber as well as their hypotensive action on the intraocular pressure. The results obtained showed that, when Ap4A was topically applied two hours before the adrenergic compounds, the concentration of brimonidine in the aqueous humour increased from 64.3±5.3nM to 240.6±8.6nM and from 58.9±9.2nM to 183.7±6.8nM in the case of timolol, which also produces a more profound effect on IOP. Therefore, Ap4A treatment results in a better entrance of adrenergic anti-glaucomatous compounds within the eye and consequently improved therapeutic efficiency by increasing corneal epithelial barrier permeability


Item Type:Article
Additional Information:

Received 17 November 2014 / Received in revised form 28 January 2015 /Accepted in revised form 17 February 2015 / Available online 19 February 2015

Uncontrolled Keywords:Brimonidine; Corneal epithelium; Diadenosine tetraphosphate; Drug delivery; Glaucoma; Intraocular pressure; Tight junction; Timolol
Subjects:Medical sciences > Medicine > Medical microbiology
Medical sciences > Medicine > Ophtalmology
Medical sciences > Pharmacy > Pharmacology
ID Code:41000
Deposited On:26 Jan 2017 09:02
Last Modified:26 Jan 2017 11:07

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