May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Spatial and Temporal Regulation of Corneal Innervation During Chicken Embryonic Development
Author Affiliations & Notes
  • J. K. Kubilus
    Cell, Molecular and Developmental Biology Program, Tufts University Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts
  • T. F. Linsenmayer
    Anatomy and Cell Biology, Tufts University School of Medicine, Boston, Massachusetts
  • Footnotes
    Commercial Relationships J.K. Kubilus, None; T.F. Linsenmayer, None.
  • Footnotes
    Support NEI Grant EY05191; NIH 5T32-HD007403-14
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3463. doi:
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      J. K. Kubilus, T. F. Linsenmayer; Spatial and Temporal Regulation of Corneal Innervation During Chicken Embryonic Development. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3463.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: The corneal epithelium is one of the most highly innervated structures in the body. During embryonic development the cornea undergoes several well-defined steps in order to form the mature structure necessary for the protection of the eye and proper vision. Sensory innervation by neurons from the opthalmic branch of the trigeminal ganglion is necessary for the maintenance of a healthy adult cornea. Our goal is to elucidate the molecular regulation of axon guidance into the cornea during development.

Methods:: The spatial and temporal growth of axons into the cornea was determined using immunohistochemistry in chickens between embryonic day 6 (E6) and E14. Expression of axon guidance molecules in the anterior eye and their receptors in the opthalmic branch of the trigeminal ganglion were determined using qRT-PCR and in situ hybridization. To study the mechanisms involved in regulating corneal innervation corneal and trigeminal ganglion explants were co-cultured in 3-dimensional collagen gels.

Results:: Developmentally, between E6 and E10 axons form a peri-corneal ring in the limbus surrounding the cornea. At E10 these axons radially enter the corneal stroma and at E12 they make a 90-degree turn, penetrate Bowman’s membrane and subsequently enter the corneal epithelium. The expression of several axon guidance molecules suggests they are involved in the temporal and spatial regulation of axon growth into the cornea. The expression of semaphorin 3A, an axon repulsive cue, is increased in the cornea at E6 compared to E13. Also, the expression of brain derived neurotrophic factor, a positive neurotrophic cue for axons, is increased at later timepoints in the cornea. In 3-dimensional co-cultures axons from E8 trigeminal ganglia failed to innervate E13 corneas, suggesting that changes in the neurons themselves are also important in corneal innervation.

Conclusions:: Axon guidance into the cornea is spatially and temporally regulated by cues from the cornea as well as by changes within the trigeminal neurons themselves.

Keywords: cornea: basic science • innervation: sensation • development 

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