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Patrick Shean-Young Lee, Nan Gao, Fushin X Yu; Role of Semaphorin 3C and its Receptor, Neuropilin-2, in Impaired Sensory Nerve Regeneration and Wound Healing in the Diabetic Mouse Cornea. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4348.
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Class 3 Semaphorins are secreted proteins that control axonal branching and pathfinding in the nervous system. This study sought to investigate the role of Sema3C, one member of the class 3 Semaphorins, and Nrp2, its receptor, in epithelium innervation in homeostatic corneas and re-innervation in post-wound corneas of normal and diabetic mice.
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 functional antibodies for receptor blockade were subconjunctivally injected prior to epithelium-wounding. Sensory nerve fibers/endings were assessed by whole mount confocal microscopy.
Corneal epithelial expression of Sema3C was 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. Expression of Nrp2, a receptor for Sema3C, was induced in healing corneal epithelium, and this increase was also suppressed in diabetic healing cornea. Sema3C knockdown by subconjunctival siRNA injections in wounded mice resulted in a decrease in the rate of wound healing and a decrease in regenerating nerve fibers. Antibody-mediated blockade of Nrp2 resulted in similar decreases in nerve regeneration and rate of wound healing.
Epithelium expressed Sema3C plays a role in the maintenance and post wound regeneration of sensory nerve fibers/endings. The hyperglycemia-suppressed expression of Sema3C, by binding through the nrp2 receptor, 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 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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