Abstract
Purpose: :
Although corneal innervation has been well studied in adults, little is known about the development of mammalian corneal nerves.
Methods: :
We carefully examined corneal innervation at different stages of mouse eye development. Embryos were collected at various stages of development including embryonic day (E)12-E16, postnatal (P)0, P10, P21, and adult. Embryos and dissected corneas were immunostained with a neuron specific betta III tubulin antibody. Fluorescently labeled nerves in whole-mount tissues and sections at each developmental stage were imaged and analyzed for axon projections.
Results: :
The first nerve bundles appear at the periphery of the cornea at E12.5. Initial projections into the stroma occur at E13.5 without formation of a pericorneal nerve ring. Between E13.5-E16.5, four major nerve bundles from specific peripheral locations project directly into the presumptive cornea and branch repeatedly as they innervate the anterior two thirds of the stroma. First epithelial innervation occurs at about E16.5 and increases between E16.5-P0. Subbasal nerves become organized into leashes that project towards the cornea center, subsequently forming a swirl at P21 close to the cornea apex.
Conclusions: :
Our results document the spatiotemporal behavior of axon projections during mouse corneal innervation. We observe major differences between the mouse and the published avian corneal innervation. The data provide a basis for further studies using the mouse as a model organism for corneal innervation.
Keywords: cornea: basic science • development • innervation: sensation