UK Keratoconus Self-Help and Support Association

Involvement of Corneal Nerves in the Progression of Keratoconus

Researchers at the University of Auckland, New Zealand, believe that studying the process of extracellular matrix remodeling from studies of connective tissues other than the cornea and from wound healing studies in the cornea can provide insight into the molecular mechanisms of keratoconic disease pathogenesis and progression.

The researchers previously developed a new approach to studying keratoconus based on the observation that there is a gradient of damage across the keratoconic cone. They identified a number of cellular characteristics of keratoconus, such as discrete incursions of fine cellular processes from the anterior keratocytes in association with localized indentation of the basal epithelium, and increased levels of the lysosomal enzymes Cathepsin B and G in aberrant keratocytes, located beneath compromised regions of Bowman's layer and deeper in the stroma. Enzyme activity by these cells appeared to cause localized structural degradation of the anterior stroma, leading to near-complete destruction of Bowman's layer and the stroma. This often necessitated a full-thickness corneal graft for sight restoration. The current study extended their initial findings by investigating the role of corneal nerves passing between the stroma and epithelium at the sites of early degradative change observed previously.

Cells in sections of normal and keratoconic human corneas were labeled with the fixable fluorescent viability dye 5-chloromethylfluorescein diacetate, antibodies to alpha-tubulin (nerves), alpha3beta1 integrin, Cathepsin B and G and the nuclear dye DAPI. They were then examined with a confocal microscope. Anterior keratocyte nuclei were seen wrapping around the nerves as they passed through the otherwise acellular Bowman's layer, and as the disease progressed and Bowman's layer degraded, these keratocytes expressed higher levels of Cathepsin B and G, and became displaced anteriorly into to the epithelium. Localized nerve thickenings also developed within the epithelium in association with Cathepsin B and G expression, and appeared to be very destructive to the cornea. The authors believe that additional studies will help determine how well this model fits the actual molecular basis of the pathogenesis of keratoconus.