Variable Involvement of the Perivascular Retinal Tissue in Carbonic Anhydrase Inhibitor–Induced Relaxation of Porcine Retinal Arterioles In Vitro

Kehler, Anne Katrine; Holmgaard, Kim; Hessellund, Anders; Aalkjær, Christian; Bek, Toke

doi:10.1167/iovs.07-0048

Cited by 21 publications

(15 citation statements)

References 22 publications

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“…The experiments of the present study extend previous studies using the wire myograph to investigate the tone regulation of retinal arterioles. 6,14,15 Adenosine was shown to induce vasorelaxation that was independent of the presence of perivascular tissue, indicating a direct effect on the arteriolar wall. In previous studies it has been shown that 8-PSPT can reduce this relaxing effect 6 and that the vasodilating effect of adenosine on isolated porcine retinal arterioles is mediated by A 2A receptors but not by A 1 receptors.…”

Section: Discussionmentioning

confidence: 99%

Dual Effects of Adenosine on the Tone of Porcine Retinal Arterioles In Vitro

Riis-Vestergaard¹,

Misfeldt²,

Bek³

2014

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 99%

Dual Effects of Adenosine on the Tone of Porcine Retinal Arterioles In Vitro

Riis-Vestergaard¹,

Misfeldt²,

Bek³

2014

Invest. Ophthalmol. Vis. Sci.

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“…The vasorelaxing effect of dorzolamide was signifi cantly reduced in isolated arterioles, as evidenced by both a reduction in the maximum relaxation and an increase in EC 50 . 42 It is therefore highly likely that the vasorelaxing effect of these drugs depends on carbonic anhydrases in the perivascular tissue. This effect may have involved different membrane-bound isoenzyme IV and XIV located in retinal astrocytes and Müller cells.…”

Section: Discussionmentioning

confidence: 99%

A Comparison of the Long-Term Effects of Dorzolamide 2% and Brinzolamide 1%, Each Added to Timolol 0.5%, on Retrobulbar Hemodynamics and Intraocular Pressure in Open-Angle Glaucoma Patients

Martínez

Sánchez-Salorio²

2009

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To compare the effect on the retrobulbar hemodynamics and intraocular pressure (IOP) of dorzolamide 2% and brinzolamide 1%, each added to timolol 0.5% in patients with primary open-angle glaucoma (POAG). Methods: 146 POAG patients were prospectively randomized to receive either dorzolamide 2% or brinzolamide 1% BID, each added to timolol 0.5%, during a 60-month evaluator-masked study. At baseline and every 6 months for 60 months, we measured the retrobulbar hemodynamic parameters in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCA) using color Doppler imaging (CDI), intraocular pressure (IOP), and blood pressure measurements. Results: Dorzolamide signifi cantly increased the end-diastolic velocity (EDV) in the OA in 1.22 cm/s, 95% confi dence interval (95% CI) 0.90-1.56 cm/s, P < 0.001 and reduced the resistivity index (RI) in the OA in 0.04 units, 95% CI 0.03-0.05, P < 0.001. None of the retrobulbar parameters changed signifi cantly on therapy with brinzolamide when the results were analyzed at month 60. Both dorzolamide and brinzolamide signifi cantly decreased IOP (-4.3, 95% CI -4.5 to -4.2 mmHg and -4.3, 95% CI -4.4 to -4.2 mmHg, respectively). Dorzolamide significantly reduced the RI in the OA from 0.74 (0.02) to 0.70 (0.02), CRA from 0.66 (0.02) to 0.62 (0.02), and SPCA from 0.66 (0.02) to 0.62 (0.02), P < 0.001, respectively. Conclusions: Our results suggest augmented retrobulbar blood fl ow after 5 years of treatment with dorzolamide but not with brinzolamide, each added to timolol, in POAG patients.

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“…The diffusion distance from the point of drug application (the cornea) to the ciliary body is much shorter than the distance to the posterior choroid measurement site, and so greater drug delivery may explain the more robust ciliary response. However, dorzolamide’s vascular mechanism of action is presumed to be caused by tissue hypercapnia or changes in local pH, 21,22,46 and the greater amount of metabolically active tissue adjacent to the resistance arterioles in the ciliary body than in the choroid may also contribute to the discrepant vascular effects.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 In vitro studies also show a direct vasodilatory effect of CAIs on retinal arterioles. 21,22 Given the ambiguity in the reported ocular blood flow responses to dorzolamide, one goal of the present study was to determine its effects on choroidal and ciliary blood flow at different perfusion pressures in an established rabbit model, 23,24 which had not been done previously.…”

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confidence: 99%

Effects of Dorzolamide on Choroidal Blood Flow, Ciliary Blood Flow, and Aqueous Production in Rabbits

Reitsamer

Bogner

Tockner

et al. 2009

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine the effects of topical dorzolamide (a carbonic anhydrase inhibitor) on choroidal and ciliary blood flow and the relationship between ciliary blood flow and aqueous flow. Methods The experiments were performed in four groups of pentobarbital-anesthetized rabbits treated with topical dorzolamide (2%, 50 μL). In all groups, intraocular pressure (IOP) and mean arterial pressure (MAP) at the eye level were measured continuously by direct cannulation. In group 1, aqueous flow was measured by fluorophotometry before and after dorzolamide treatment. In group 2, aqueous flow was measured after dorzolamide at normal MAP and while MAP was held constant at 80, 55, or 40 mm Hg with occluders on the aorta and vena cava. In group 3, the same MAP levels were used, and ciliary blood flow was measured transsclerally by laser Doppler flowmetry (LDF). In group 4, choroidal blood flow was measured by LDF with the probe tip positioned in the vitreous over the posterior pole during ramp increases and decreases in MAP before and after dorzolamide. Results Dorzolamide lowered IOP by 19% (P < 0.01) and aqueous flow by 17% (P < 0.01), and increased ciliary blood flow by 18% (P < 0.01), which was associated with a significant reduction in ciliary vasculature resistance (−7%, P < 0.01). Dorzolamide shifted the relationship between ciliary blood flow and aqueous flow downward relative to the previously determined control relationship in the rabbit. Dorzolamide did not alter choroidal blood flow, choroidal vascular resistance, or the choroidal pressure flow relationship. Conclusions Acute topical dorzolamide is a ciliary vasodilator and has a direct inhibitory effect on aqueous production, but it does not have a detectable effect on choroidal hemodynamics at the posterior pole in the rabbit.

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Variable Involvement of the Perivascular Retinal Tissue in Carbonic Anhydrase Inhibitor–Induced Relaxation of Porcine Retinal Arterioles In Vitro

Cited by 21 publications

References 22 publications

Dual Effects of Adenosine on the Tone of Porcine Retinal Arterioles In Vitro

Dual Effects of Adenosine on the Tone of Porcine Retinal Arterioles In Vitro

A Comparison of the Long-Term Effects of Dorzolamide 2% and Brinzolamide 1%, Each Added to Timolol 0.5%, on Retrobulbar Hemodynamics and Intraocular Pressure in Open-Angle Glaucoma Patients

Effects of Dorzolamide on Choroidal Blood Flow, Ciliary Blood Flow, and Aqueous Production in Rabbits

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