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JL Bennett, MM Boulter, Z Baquet, KR Jones; Trigeminal Axon Branching Is Reduced In The Corneas Of Neurotrophin-3 Hypomorphic Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3224.
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Purpose: Neurotrophin-3 (NT-3) supports the survival, outgrowth, and maturation of various neuronal cell populations. NT-3 is expressed at high levels in the developing and mature corneal epithelium where its function remains unclear. To elucidate the role of NT-3 in corneal epithelium, we examined the innervation and response to noxious stimuli of corneas from NT-3 hypomorphic (NT-3lox/lox) animals. Methods: We examined the anatomic and functional innervation of corneas from postnatal day 15 (P15) and adult (P42) wild type (wt), NT3lox/+, and NT-3lox/lox animals. Axonal branching was quantified by anti-peripherin and anti-PGP9.5 immunocytochemistry. Functional innervation was assayed by blink response to a variety of noxious stimuli: mechanical depression, acid, temperature, and capsaicin. NT-3 levels in ocular tissue were measured by ELISA (Promega). Results: (A) Immunocytochemistry of corneas from P15 and adult wt, NT3lox/+, and NT-3lox/lox animals revealed significantly reduced axonal branching in NT-3lox/lox animals (P15: NT-3lox/lox/wt; p < .001; NT-3lox/lox/NT-3lox/+; p < .001 and Adult: NT-3lox/lox/wt; p < .005; NT-3lox/lox/NT-3lox/+; p < .01). Reduced axonal branching was demonstrated with both anti-peripherin and anti-PGP9.5 staining and correlated with diminished NT-3 tissue levels. (B) Functional testing of corneal innervation revealed a significant reduction in blink response to mechanical stimulation in NT-3lox/lox and NT-3lox/+ animals (p < .05). No difference was noted in blink response to stimulation with acetic acid, temperature, or capsaicin. Conclusion: Reduced NT-3 expression results in diminished trigeminal axonal branching and diminished blink response to mechanical stimuli. Interestingly, a similar branching deficiency is observed in the sympathetic innervation of the pineal gland in NT-3+/- heterozygous mice. NT-3 expression in peripheral target tissue may play an important role in directing neuronal branching, and modulation of corneal NT-3 expression may be beneficial following neuropathic injury.
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