Ultrastructural organization of human corneal nerves.

PURPOSE Although the human cornea is densely innervated, observations of the nerve fiber distribution and ultrastructure are scarce. This study aimed to provide a detailed electron microscopic analysis of nerve fibers in the central and peripheral human cornea. METHODS Samples from seven fresh corneas, obtained from the eyes of persons with melanoma, were processed for light and electron microscopic examinations. Both frontal and cross-sections were studied. Furthermore, serial ultrathin sections from the mid-epithelium to the anterior stroma were used. RESULTS Unmyelinated nerve fiber bundles (as many as 30 nerve fibers and cross-section as large as 20 micrometers) run parallel to the stromal collagen fibers. Nerve fibers contain clear, dense cored and dense vesicles and are ensheathed by thin rims of Schwann cell protrusions and amorphic matrix. Some nerve fibers invaginate the cytoplasm of keratocytes. After passing through Bowman's membrane, bundles of straight fibers (cross-section 0.1 to 0.5 micrometers) and single-beaded nerve fibers, which both lack Schwann cell ensheathment, run parallel in an alternating manner. Beaded nerve fibers, containing many mitochondria and glycogen (cross-section as large as 2 micrometers), turn upward and invaginate both basal and wing cells. Except for the presence of myelinated nerve fibers in the peripheral stroma, no differences in the central cornea were observed. CONCLUSIONS Nerve fibers invaginating epithelial cells and keratocytes suggest that both cell types are directly innervated. The presence of vesicles, mitochondria, and glycogen in stromal and epithelial nerve fibers suggest that classical and peptidergic transmitters, probably of sensory origin, innervate the human cornea. Peptidergic transmitters in nerve fibers may be involved in neuroimmunomodulation of the cornea.