Innervation of the mouse cornea during development.
OBJECTIVE
Dense innervation of the cornea is important for maintaining its homeostasis and transparency. Although corneal nerves have been well studied in adults, little is known about mammalian corneal innervation during development. This study provides a detailed profile of nerves at various stages of mouse cornea development.


METHODS
Mouse heads and corneas were collected at various stages of development including embryonic days (E)12.5 to E16.5, postnatal days (P)0, P10, three weeks after birth, and the adult. Corneas were immunostained with an anti-neuron-specific β-tubulin antibody (TUJ1). Fluorescently labeled nerves in whole-mount tissues and sections were imaged and analyzed for their axonal projections during eye development.


RESULTS
The first nerve bundles appear at the periphery of the anterior portion of the eye by E12.5. Initial projection into the stroma occurs at E13.5 without formation of a pericorneal nerve ring. Between E13.5 and E16.5, nerve bundles project directly into the periphery of the presumptive cornea stroma. They branch repeatedly as they extend toward the cornea center and epithelium. Concomitantly, nerve bundles originating from four quadrants of the eye bifurcate into smaller branches that innervate the entire stroma. The first epithelial innervation occurs at E16.5. Epithelial nerves arrange into patterns that project toward the center subsequently forming a swirl at three weeks after birth, which becomes more pronounced in adults.


CONCLUSIONS
Nerve bundles that arise from four quadrants of the eye innervate the mouse cornea. The nerve bundles directly innervate the stroma without forming a pericorneal nerve ring. Radial arrangement of epithelial nerves gradually becomes centrally oriented, subsequently forming a swirl pattern.
McKenna
Chelsey C
CC
Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA.
Lwigale
Peter Y
PY
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D003315:Cornea / Q000196:embryology* / Q000294:innervation*; D003319:Corneal Stroma / Q000196:embryology / Q000294:innervation; D047108:Embryonic Development / Q000502:physiology*; D019573:Epithelium, Corneal / Q000196:embryology / Q000294:innervation; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009882:Ophthalmic Nerve / Q000033:anatomy & histology* / Q000196:embryology* / Q000502:physiology; D014404:Tubulin / Q000378:metabolism
D014404:Tubulin; C462941:beta3 tubulin, mouse
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