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Jesus Merayo-Lloves, Ignacio Alcalde, Juana Gallar, Cruz Morenilla-Palao, Susana del Olmo, Carlos Belmonte; Age-related Changes in Density and Morphology of Corneal Cold Nerve Fibers. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1973.
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Basal tearing is modulated by the activity of corneal cold thermoreceptors expressing the TRPM8 cold transduction channel (Parra et al. Nat. Med. 2010). The aim of this study is to examine the change in density and morphology of corneal cold nerve fibers related to aging and to correlate corneal cold nerve density and tear production.
Corneas from adult transgenic TRPM8-EYFP mice with ages ranging from 3 months (P90) to 1 year (P360) were studied using double immunostaining techniques against TuJ1 and GFP, on whole mounted corneas. Tuj1 stains all sensory nerve fibers while GFP distinguishes selectively TRPM8-positive, putative cold nerve fibers. Basal tear production was measured periodically along the lifespan of the animals, using Phenol Red threads.
A progressive reduction in the number of TRPM8-EYFP cold nerve terminals, seen as pencillated endings in the outermost layers of the epithelium was observed in mice of increasing ages. This decrease was less evident for terminals that were only TuJ1 positive which appeared as thin, elongated filaments at the surface of the cornea. TRPM8 cold nerve terminals retract with age towards deeper layers of the epithelium, exhibiting a prominent beaded morphology. Basal tear secretion was also lower in old mice in comparison with young animals.
The parallelism between reduction with age of cold nerve terminal density in the outer layers of the corneal epithelium and the decrease in basal tear production in old animals, supports the hypothesis that sensory inflow from TRPM8-positive cold fibers of the cornea play a role in the determination of basal tear flow and in the decreased tear production observed in aged individuals.
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