Corneal Innervation

The cornea is the most densely innervated tissue of the body. For comparison, the cornea has 300-600 times the sensory innervation density of the skin. This dense innervation is necessary since the cornea is the first line of defense against injury to the eye. These nerves prevent you from “poking your eye out.” But equally as important, the corneal nerves produce neurotrophins that are essential to maintain a healthy and transparent cornea.

Nerves in the cornea can be lost from surgery (Lasik has shown to decrease nerve density by 40%), injury to the cornea or trigeminal nerve, or other diseases. When there is not an appropriate density of nerve bundles in the cornea, disease states such as dry eye, corneal ulcers or neurotrophic keratitis can start to hinder proper vision. Our lab hopes to understand how nerves originally develop in the cornea, and discover which molecules help to regulate this development so we can increase the treatment arsenal available to help rebuild cornea nerves.

The vast majority of corneal nerves are sensory and derive from the ophthalmic division of the trigeminal ganglion. These nerves have been intensely studied in many species for over 100 years, but almost all of these studies have been conducted on adult corneas. The development of innervation was well studied in the chick in the1980s and has been used as a reference ever since. In the avian system, cornea nerves approach the eye in the ventrotemporal region and start to surround the cornea with a dorsal and a ventral branch until a ring of nerve fascicles is formed that completely surrounds the cornea in just a few days. After the ring is formed, the fascicles start to innervate the cornea in a radial manner at multiple positions. These fascicles enter at approximately the mid-stoma and travel toward the center of the cornea and start to innervate the epithelium.

This model of cornea nerve development has been assumed to be the same for all species. However, our lab discovered that this is not the case. We found that the mouse eye does not form a pericorneal nerve ring, but instead starts to innervate the cornea directly from four major branches.

Chick and mouse cornea innervation
Chick corneal nerve ring shown in green on the left. Innervation of the embryonic mouse cornea from 4 major branches, shown in red on the right. Dotted lines delineate the cornea.

 

The differences seen in cornea nerve development raise many interesting questions. We are actively determining if the same molecules that control the development of innervation in the chick also play a role in mammalian corneal innervation, or if there are different molecular regulators at play here.  The results may shed light on how injured corneas can be properly re-innervated in the adult.