Abstract
Purpose: :
To determine the effects of desiccating stress on corneal nerve regeneration in a mouse model of dry eye.
Methods: :
Dry eye was induced in female C57BL/6 mice (n=20) by exposure to the controlled environment chamber and to systemic scopolamine. Age-matched mice (n=20) that were not exposed to desiccating stress served as controls. After 2 days, partial thickness trephinations were made in corneas of both groups using a 2-mm corneal trephine to sever nerve bundles. Corneas were harvested on days 3-10. Corneal wholemounts immunostained with anti-mouse ß III tubulin were prepared and imaged using confocal immunofluorescence microscopy.
Results: :
On early days after trephination (days 3-5), the neuronal processes distal to the cut were barely detectable both in dry eye and control groups. However, on later time points (days 6-10), the patterns of regenerated nerve processes that sprouted from the proximal end of the severed nerve bundle were significantly different in the two groups. In the control group, there were arrays of newly regenerated nerves in the sub-basal area which exhibited paralleled and continues nerve growth towards the center of the cornea (represented by micrograph A). Minor nerve tortuosity was also visible. In contrast, the corneas in the dry eye group showed very scattered irregular nerve regeneration resembling a more bush-like pattern which hardly ever extended into the central cornea (represented by micrograph B). Moreover, nerve sprouts were highly tortuous with significant branching, and increased bead-like formation.
Conclusions: :
Sub-basal corneal nerve regeneration pattern in response to desiccating stress tends to be more different from the original nerve architecture than the non-dry eye control group.
Keywords: cornea: tears/tear film/dry eye • regeneration