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J. Zhao, W. Zhang, T. Nagasaki; Dynamics of the Corneal Nerves in a Living Mouse Eye. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3461.
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We previously hypothesized that subepithelial nerves of the cornea provide directional guidance to homeostatic movement of epithelial cells, based on histological observations. In this study, we investigated dynamics of corneal nerves and epithelial cells, asking: 1) whether the pattern of subepithelial nerve plexuses is stable in a normal cornea where epithelial cells exhibit constant centripetal movement, 2) whether a nerve injury alters the homeostatic epithelial cell movement.
GFP mice (GFP driven by a beta-actin promoter) and CFP mice (CFP driven by a thy-1 promoter) were used to monitor movement of epithelial cells and nerve cells, respectively, employing histology and in vivo time-lapse fluorescence microscopy. For the latter, digital images of GFP positive epithelial cells and CFP positive nerves were recorded up to one year at intervals of one to four weeks. Two nerve injury models were used: 1) sympathetic denervation by superior cervical ganglionectomy, 2) sensory nerve damage by subcutaneous injection of capsaicin into 2-day old mice.
In adult CFP mice, distribution patterns of anterior stromal nerves remained unchanged for over one year. Subepithelial nerve plexuses were also generally stationary, with only a minimal level of remodeling, despite the constant centripetal movement of overlying epithelial cells. Spontaneous appearance of unique epithelial cell movement patterns, such as central vortexes, was always associated with the presence of nearly identical patterns of underlying subepithelial nerves. Neuronal changes after sympathetic denervation occurred mostly at the sub-epithelial level, and there was initial degeneration followed by partial recovery of the fibers which decreased in number but maintained their radial orientation. Coincidentally, there was no observable change in the centripetal movement of epithelial cells. Capsaicin caused scar formation at the central cornea, which was occasionally accompanied by neovascularization. Both epithelial cells and nerve fibers lost their central vortex pattern, but the centripetal movement of epithelial cells and the radial orientation of subepithelial nerves remained unchanged.
Corneal nerves establish a stable network structure at an early age that remains at the same location over an extended period, possibly for life. There is a correlation between the orientation of subepithelial nerves and the direction of homeostatic epithelial cell movement. These results are in line with the hypothesis that corneal subepithelial nerves guide homeostatic movement of epithelial cells.
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