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M. E. Fitzgerald, C. Li, A. J. Reiner; Potentiation of Parasympathetic Evoked Vasodilation of the Pigeon Choroid via the Carbonic Anhydrase Inhibitor, Trusopt®. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3261. doi: https://doi.org/.
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Carbonic anhydrase inhibition with dorzolamide has been utilized to reduce intraocular pressure in glaucoma. Dorzolamide (DZ) also decreases vascular resistance and increases blood flow in the central retinal artery, posterior ciliary arteries and choroid. In the present study, we examined if DZ affects neurogenic regulation of choroidal blood flow (ChBF). These studies were carried out in pigeons, in which we have previously demonstrated that activation of the parasympathetic preganglionic nucleus Edinger-Westphal (EW) causes endothelial NO-dependent cholinergic choroidal vasodilation (Zagvazdin et al. EER 2000). In the current study, we examined the impact of acute application of Trusopt® (2% dorzolamide, DZ) on EW-evoked increases in ChBF.
ChBF was measured transclerally from the superior aspect of the pigeon eye using laser Doppler flowmetry. An insulated stainless steel stimulating electrode was sterotaxically placed in EW ipsilateral to the eye used for ChBF recording. Basal ChBF and EW-evoked responses were measured before and after a single drop of DZ (approximately 70µl) was applied to the sclera underlying the laser Doppler probe. Accuracy of electrode placement in EW was confirmed histologically after the recording session.
EW stimulation prior to DZ yielded a 40% ChBF increase, and the increase was sustained for at least 15 seconds after discontinuation of EW stimulation. DZ did not have a consistent effect on basal ChBF, but did dramatically affect the response to EW stimulation. DZ potentiated the magnitude of the EW-evoked vasodilation, and at least doubled the duration and magnitude of the ChBF increase that occurred after cessation of the EW stimulating current. The DZ-mediated potentiation of the ChBF increase during and after the EW stimulation was mediated by a large increase in blood velocity.
The present findings show that acute DZ potentiates parasympathetic increases in ChBF, via a facilitatory effect on choroidal blood velocity. The basis of the effect on blood velocity is unclear, but DZ has been shown to increase blood velocity via decreased vascular resistance in human central retinal artery (Uva et al. 2006). Since declines in ChBF and its neurogenic control that might be pathogenic occur in such ocular diseases as AMD and glaucoma, dorzolamide may offer a therapeutic benefit by its ability to potentiate (and perhaps normalize) neurogenic control of ChBF so it better meets retinal need.
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