Developmental corneal innervation: interactions between nerves and specialized apical corneal epithelial cells

The corneal epithelium is one of the most highly innervated structures in the body, and proper innervation is necessary for corneal maintenance and sensation. However, little is known about how these nerves function and how innervation occurs developmentally. The authors have examined certain aspects of corneal innervation in the developing chicken embryo.

DiI was used to determine the source of the neurons responsible for innervating the cornea. Immunohistochemistry, electron microscopy, and immunoelectron microscopy were used to examine corneal innervation and the relationships that develop between nerves and corneal epithelial cells.

Corneal nerves in the embryonic chicken originate entirely from the ophthalmic lobe of the trigeminal ganglion. Within the cornea the nerves interact with apical corneal epithelial (ACE) cells to form specialized structures that are synapse-like because they contain accumulations of vesicles and have the SV2 synaptic vesicle protein. These ACE cells themselves have unique characteristics, including transient expression of the neuronal isoform of class III beta-tubulin and formation of extensive intercellular channels and clefts that contain these specialized synapse-like structures and nerves; in addition, they are mitotically active. Given that these ACE cells react with a monoclonal antibody against this neuronal isoform of beta-tubulin (the TuJ-1 antibody), we have termed them TuJ-1(+)ACE cells.

During avian corneal development the nerves make close associations with a specialized type of ACE cell. There they form synapse-like structures, suggesting that not all nerves within the CE terminate as free nerve endings.