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Patrick Shean-Young Lee, Fushin X Yu; Role of Semaphorin 3C in Impaired Sensory Nerve Regeneration and Wound Healing in the Diabetic mouse Cornea. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6156.
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© ARVO (1962-2015); The Authors (2016-present)
Class 3 Semaphorins are secreted proteins that control axonal branching and pathfinding in the nerve system. This study sought to investigate the role of Sema3C, one member of the class 3 Semaphorins, in epithelium innervation in homeostatic corneas and re-innervation in post-wound corneas.
Corneas were wounded by debridement and allowed to heal in vivo. Fluorescein staining was used to assess wound size after debridement. SiRNAs for gene knockdown and recombinant protein were subconjunctivally injected prior to epithelium-wounding. Sensory nerve fibers/endings were assessed by whole mount confocal microscopy.
Corneal epithelial expression of Sema3C was found to be increased after wounding in normal B6 mice, as shown by real-time PCR, western blotting, and immunohistochemistry. This increase in expression was blunted in streptozotocin-induced diabetic B6 mice after wounding. Conversely, Sema3C knockdown by subconjunctival siRNA injections in wounded mice resulted in a decrease in regenerating nerve fibers as well as a decrease in the rate of wound healing. The presence of recombinant Sema3C in wounded mice led to an increase in regenerating nerve fibers. Finally, multiple injections of Sema3C siRNA every other day led to the degeneration of sensory nerves in unwounded corneas.
Sema3C expressed in corneal epithelial cells plays a role in the maintenance and post wound regeneration of sensory nerve fibers/endings. The hyperglycemia-suppressed expression of Sema3C may be responsible in part for diabetic neurotrophic keratopathy and delayed wound healing and sensory nerve regeneration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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