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Omar González González, Ignacio Alcalde, Almudena Íñigo-Portugués, Juana Gallar, Jesus Merayo-Lloves, Carlos Belmonte; REDUCED NUMBER AND ALTERED FUNCTIONAL ACTIVITY OF MOUSE CORNEAL COLD SENSORY NERVE FIBERS WITH AGE DEVELOP IN PARALLEL WITH DECREASED BASAL TEARING. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3665.
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To determine in mice the effect of ageing on the number, morphology and electrophysiological properties of corneal cold sensory nerve axons and their influence on basal tearing rate.
TRPM8-EYFP mice of different ages (3, 6, 9, 12, 18 and 24th months) were studied. Basal tearing was measured in anesthetized animals, using phenol red threads. Corneal nerves expressing EYFP protein and neuronal class III beta-tubulin were identified in whole mount corneas using immunocytochemical techniques. Density of subasal nerve branches and epithelial terminals was measured in the peripheral and central regions of the cornea. Trigeminal ganglion (TG) corneal neurons, labelled with fast blue applied onto the cornea in anesthetized mice, were identified in TG sections using immunofluorescence and counted. Extracellular electrical activity of single sensory nerve endings of the corneal surface was recorded in excised and superfused eyes.
In 3-months mice, TRPM8+ subbasal nerve fibers represent 22,4% of the total number of sub-basal nerve branches; most of them were beaded axons finally ramifying in the uppermost epithelium as a cluster of beaded nerve terminals. Less abundant, longer and narrower fibers lacking beads and ending as a single or double bulbous terminal branch were also found. The total number of TRPM8+ subbasal nerve filaments and epithelial terminals decreased non-linearly with age. 3-months mice had 37% of low-threshold (>30.5 °C) cold sensitive fibers showing high background activity and vigorous firing responses to cooling. They were reduced to 26% in 24 months-old mice. Contrarily, cold sensitive fibers with a high cooling threshold (<30.5 °C), very low frequency background activity and weak responses to cooling was 17% in 3 months-old mice and 40% in 24 months-old mice. Basal tearing values also decreased with age (3months= 1.9 ± 0.2 mm; 24months= 1.3 ± 0.2 mm) varying in parallel with the number of TRPM8 subbasal branches and epithelial terminals.
Reduction in the number and branching pattern of corneal low-threshold cold sensitive fibers with age seems to be associated with a lowering of the tearing rate, thus supporting the hypothesis that sensory input from ocular surface cold thermoreceptors contributes to the maintenance of basal tearing.
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