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Purpose To analyze the morphological changes of corneal nerves and its influence on corneal epithelial wound healing in a lacrimodeficient dry eye model in the guinea‐pig. Methods Corneal nerve architecture and the rate of corneal epithelial wound healing were studied in guinea‐pigs to whom the main lacrimal gland was removed 4 weeks before (dry eye) and in control animals. Eyes were fixed, cryoprotected and incubated with neuronal class III Beta‐tubulin antibody. Epithelial migration rate (EMR) and estimated time of healing (ETH) were calculated for 2mm‐diameter epithelial corneal debridations stained with fluorescein, photographed regularly until complete closure and analyzed with image processing software. Results Density (16±6 vs 27±11 nerves/mm2) and length (115±45 vs 186±74 µm) of subbasal nerves decreased significantly in dry eye. Subbasal nerves were less branched and tortuous. Epithelial nerve terminals were also reduced. EMR decreased significantly (63±4 vs 110±1 µm/h) and ETH increased significantly (38.6±1.8 vs 20.1±0.1 h) in dry eye. Conclusion The morphological appearance and the decreased density, length and branches of corneal subbasal nerves are suggestive of corneal nerve degeneration at 4 weeks after lacrimal gland removal. Lacrimodeficient eyes presented also a slowing‐down in corneal epithelial wound healing suggesting an early trophic defect consecutive to nerve damage. (Supported by: SAF2008‐00529, CSD2007‐00023, BFU2008‐04425, BFU2009‐07793 and RETICS RD07/0062/0012 from Ministerio de Ciencia e Innovación, Spain, and the Leonardo da Vinci Lifelong Learning Program.) [ABSTRACT FROM AUTHOR]