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A. Navas, K. Glomski, V. L. Perez, M. I. Rosenblatt; Regeneration of Sensory Nerves in Orthotopic Corneal Allografts. Invest. Ophthalmol. Vis. Sci. 2010;51(13):786.
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To investigate the relative distribution of corneal nerves and new blood or lymph vessels following allogeneic corneal transplantation in thy1-YFP mice.
Orthotopic corneal transplantion of CD1 donor tissue into thy1-YFP (c57BL/6 background) hosts was performed under anesthesia. Evidence of corneal graft rejection, as well as the regeneration of corneal nerves was monitored by bright field and fluorescence stereomicroscopy. Mice were sacrificed and corneal wholemounts analyzed by wide field and confocal fluorescence microscopy. Distribution and morphology of regenerating nerves within the corneal stroma and in the sub-basal plexus was separately analyzed using neuron analysis software. Simultaneous imaging of blood vessels (CD-31 immunohistochemistry) and lymph vessels (LYVE-1 immunohistochemistry) was performed on these same wholemounts.
Growth of corneal nerves into the allogenic donor tissue was observed as soon as three days after transplantation and was primarily a result of sub-basal plexus nerve ingrowth from peripheral host cornea. Deeper nerve ingrowth was observed at later time points, however deeper stromal nerves displayed increased degrees of tortuosity and abnormal morphology compared to controls. At 6 months sub-basal nerve density had not reached levels seen prior to transplant and deeper nerve morphology remained aberrant. In a subset of rejected corneas, abnormal blood and lymph vessel infiltration in to the donor cornea was observed. No significant co-localization of the regenerated corneal nerves with the neoangiogenesis was observed.
Corneal nerves reinnervate donors cornea, however a decriment of corneal nerve density persists and is accompanied by longlasting changes in deep nerve morphology. New vessels and nerves seen in rejected allografts do not appear to develop along the same paths.
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