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Illes Kovacs, Susana Quirce, Carolina L. Luna, M.Carmen Acosta, Carlos Belmonte, Xavier Gasull, Juana Gallar; Cyclosporine A Decreases Hyperexcitability of Corneal Cold Receptor Terminals by Altering Action Potential Generation in Experimental Dry Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1795.
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© ARVO (1962-2015); The Authors (2016-present)
Amelioration of ocular dryness sensations and hypersensitivity induced by treatment with cyclosporine A (CSA) is attributed to an anti-inflammatory action of the drug. However, the immediate reduction of discomfort following CSA treatment suggests a direct effect of CSA on corneal nerves. To explore this possibility, we measured the effect of acute application of cyclosporine A, on the impulse activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs.
Four weeks after unilateral surgical removal of the main lacrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34 ºC for extracellular recording of nerve terminal impulse (NTI) activity of cold-thermosensitive nerve terminals. Changes in firing frequency of the spontaneous and the stimulus-evoked (cooling ramps from 34 ºC to 20 ºC) NTI activity, and in NTI shape were recorded before and during perfusion with 50µM CSA.
Compared to controls (n=13), cold nerve terminals of dry eye corneas (n=17) showed significantly enhanced spontaneous activity at 34ºC and a lower cold threshold in response to cooling ramps. Treatment with CSA did not affect the cooling threshold but decreased significantly the firing response to cold stimuli and changed nerve impulse shape (Table 1).
Cyclosporine A decreased the enhanced responsiveness to cold observed in corneal cold-sensitive nerve terminals of lacrimo-deficient guinea pigs, which appears to be due to alterations of membrane sodium currents (see poster by Gallar et al., ARVO 2012). This suggests that CSA may act directly on the action potential generation at corneal cold nerve terminals by reducing the hyperexcitability secondary to long term ocular dryness.
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