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N. Karagianni, A. Liu, S. Fukuoka, M. I. Rosenblatt; Analysis of Corneal Nerve Regeneration Following Deep vs. Superficial Injury. Invest. Ophthalmol. Vis. Sci. 2010;51(13):392.
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To characterize the regeneration of corneal nerves in thy1-YFP mice using models of deep vs. superficial corneal nerve injury.
Thy1-YFP mice under anesthesia received either a superficial injury via debridement of the epithelium and underlying sub-basal nerve plexus, or deep nerve axotomy using direct visualization of neurofluorescent large nerve bundles via fluorescence stereomicroscopy. Mice were sacrificed following injury and wholemounts imaged using wide-field and confocal microscopy to separately image nerves within the stroma and those within the sub-basal plexus. Images were analyzed using neuron analysis software to quantify axonal morphology.
Following superficial debridement, two patterns of sub-basal nerve regeneration were observed: one at the edge of the non-injured peripheral nerves and a second from beneath the debrided epithelium. Most sub-basal nerve regeneration occurred within 4 days after the initial injury with a peak density of 63% at 28 days. Deeper injury resulted in an 80% loss of sub-basal nerves within the quadrant of injury within 1 day. At day 14 the sub-basal nerve density was only 30% of control. In contrast, the deeper regeneration of nerves was more robust and approached 135% of control values. The morphology of these regenerated nerves however showed significantly greater tortuosity that the uninjured deep stromal nerves.
The regenerative response of nerves varies according to the anatomic location of injury, with deeper injury resulting in greater long-term surface nerve loss. These finding are consistent with data found for clinical damage to the corneal nerves, and the animal models used in this study may offer an opportunity for the future study of modulators of neural regeneration to treat loss of corneal nerves following injury.
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