PURPOSE: Corneal nerves play essential roles in maintaining the ocular surface through provision of neurotrophic support, but genetic control of corneal innervation is poorly understood. The possibility of a neurotrophic failure in ocular surface disease associated with heterozygosity at the Pax6 locus (aniridia-related keratopathy [ARK]) was investigated. METHODS: Patterns of corneal innervation were studied during development and aging in mice with different Pax6 dosages and in chimeras. Immunohistochemistry and ELISA-based assays were used to determine the molecular basis of defects seen in Pax6 mutants, and wound healing assays were performed. RESULTS: In adults, the Pax6(+/-) epithelium was less densely innervated than the wild-type epithelium, and radial projection of epithelial nerves was disrupted. Neurotrophic support of the corneal epithelium appeared normal. Directed nerve projection correlated with patterns of epithelial cell migration in adult wild-types, but innervation defects observed in Pax6(+/-) mice were not fully corrected in wound healing or chimeric models where directed epithelial migration was restored. CONCLUSIONS: Pax6 dosage nonautonomously controls robust directed radial projection of corneal neurons, and the guidance cues for growth cone guidance are not solely dependent on directed epithelial migration. There is little evidence that ARK represents neurotrophic keratitis.
PURPOSE: Corneal nerves play essential roles in maintaining the ocular surface through provision of neurotrophic support, but genetic control of corneal innervation is poorly understood. The possibility of a neurotrophic failure in ocular surface disease associated with heterozygosity at the Pax6 locus (aniridia-related keratopathy [ARK]) was investigated. METHODS: Patterns of corneal innervation were studied during development and aging in mice with different Pax6 dosages and in chimeras. Immunohistochemistry and ELISA-based assays were used to determine the molecular basis of defects seen in Pax6 mutants, and wound healing assays were performed. RESULTS: In adults, the Pax6(+/-) epithelium was less densely innervated than the wild-type epithelium, and radial projection of epithelial nerves was disrupted. Neurotrophic support of the corneal epithelium appeared normal. Directed nerve projection correlated with patterns of epithelial cell migration in adult wild-types, but innervation defects observed in Pax6(+/-) mice were not fully corrected in wound healing or chimeric models where directed epithelial migration was restored. CONCLUSIONS:Pax6 dosage nonautonomously controls robust directed radial projection of corneal neurons, and the guidance cues for growth cone guidance are not solely dependent on directed epithelial migration. There is little evidence that ARK represents neurotrophic keratitis.
Authors: Min Zhao; Bing Song; Jin Pu; Teiji Wada; Brian Reid; Guangping Tai; Fei Wang; Aihua Guo; Petr Walczysko; Yu Gu; Takehiko Sasaki; Akira Suzuki; John V Forrester; Henry R Bourne; Peter N Devreotes; Colin D McCaig; Josef M Penninger Journal: Nature Date: 2006-07-27 Impact factor: 49.962
Authors: Lucy J Leiper; Petr Walczysko; Romana Kucerova; Jingxing Ou; Lynne J Shanley; Diane Lawson; John V Forrester; Colin D McCaig; Min Zhao; J Martin Collinson Journal: BMC Biol Date: 2006-08-16 Impact factor: 7.431
Authors: Giulio Ferrari; Amir R Hajrasouliha; Zahra Sadrai; Hiroki Ueno; Sunil K Chauhan; Reza Dana Journal: Invest Ophthalmol Vis Sci Date: 2013-01-28 Impact factor: 4.799