Abstract
Purpose: :
Corneal nerves play a pivotal role in maintaining a healthy ocular surface. The cornea has the highest density of nerves and the highest sensitivity among all human tissues, but details of the innervation network are not well known. Here, we used a newly developed method of immunofluorescence staining and imaging (ARVO-2009) to study the effects of aging, gender, corneal transplantation and corneal dystrophy on changes in corneal nerve morphology and density.
Methods: :
We used normal human eyes (obtained from NDRI ) of both sexes (aged 19-80 years old), 2 eyes from a 59-yr-old male with corneal basement membrane dystrophy, and 2 eyes from a 63-yr-old male with bilateral penetrating transplantations for 38 yrs. Corneas from whole mounts were stained with mouse monoclonal anti-tublin III antibody and images were acquired to build the entire view of the corneal nerve architecture of both epithelia and stroma Corneal nerve density was calculated and differences in corneal epithelial nerve densities and main stromal nerve numbers were compared by analysis of variance.
Results: :
There was a 19% disparity in the number of stromal nerves between the corneas examined, but no correlation with the age or gender of the donors; no significant differences were found between the number of nerves in each of the four quadrants of the cornea. Epithelial innervations, supplied by two sources of nerve networks, did not show any difference in epithelial nerve densities between genders, but there was a progressive reduction concomitant with aging, especially after age 70. Transplantation and corneal dystrophy lead to altered nerve morphology and reduced epithelial nerve density. In the transplanted corneas, nerves from the host stroma penetrated the graft epithelium and divided into smaller branches that connected to each other. In corneal dystrophy, the stroma nerves seemed normal, but in the epithelia, pathological areas were deprived of innervation.
Conclusions: :
We show for the first time the detailed nerve architecture of the entire cornea, not only of normal tissue, but of corneas with dystrophy and after long term transplantation, revealing that these pathologies alter the epithelial nerve network.
Keywords: cornea: basic science • innervation: sensation • immunohistochemistry