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Publication : Cyclosporine immunomodulation retards regeneration of surgically transected corneal nerves.

First Author  Namavari A Year  2012
Journal  Invest Ophthalmol Vis Sci Volume  53
Issue  2 Pages  732-40
PubMed ID  22205605 Mgi Jnum  J:196792
Mgi Id  MGI:5489888 Doi  10.1167/iovs.11-8445
Citation  Namavari A, et al. (2012) Cyclosporine immunomodulation retards regeneration of surgically transected corneal nerves. Invest Ophthalmol Vis Sci 53(2):732-40
abstractText  PURPOSE: To determine whether immunomodulation with cyclosporine (CsA) affects reinnervation after surgical transection of stromal nerves. METHODS: Thy1-YFP+ neurofluorescent mice underwent lamellar corneal surgery and 3 days later, received artificial tears or CsA eye drops for 6 weeks. Serial in vivo wide-field stereofluorescent microscopy was performed to determine changes in nerve fiber density (NFD). Real-time quantitative PCR was performed to determine the expression of neurotrophins and cytokines (IL6 and TNF-alpha). Compartmental culture of trigeminal ganglion neurons was performed in Campenot devices to determine whether CsA directly affects neurite outgrowth. RESULTS: Yellow fluorescent protein (YFP)-positive cells significantly increased at 3 and 7 days after surgery. The number of YFP-positive cells in the cornea was significantly lower in the CsA group than that in the control group. The percentage increase in NFD between 2 to 6 weeks was greater in the control group (80% +/- 10%, P = 0.05) than that in the CsA group (39% +/- 21%). The CsA group also exhibited lower expression of IL6 and TNF-alpha (P = 0.01). In compartmental culture experiments, neurite outgrowth toward side compartments containing CsA was significantly less (2.29 +/- 0.4 mm, P = 0.01) than that toward side compartments containing vehicle (3.97 +/- 0.71 mm). CONCLUSIONS: Immunomodulation with CsA reduces the expression of cytokines (IL6) in the cornea and retards regenerative sprouting from transected corneal stromal nerve trunks. In addition, CsA has a direct growth inhibitory action on neurites as well.
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