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Vivian Lee, Chenyan Lin, Robyn Y. Kweon, Xiaoping Yang, Tzvete Dentchev, John Seykora; Increased SFK activity enhances wound healing in neurotrophic keratopathy mouse model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5096. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal nerves play a critical role in corneal epithelial wound healing. In neurotrophic keratopathy, corneal innervation by the trigeminal nerve is impaired, leading to nonhealing ulcers, opacities, and in severe cases corneal blindness. Src-family kinases (SFK) are a family of non-receptor tyrosine kinases involved in epithelial migration, proliferation, and differentiation. The purpose of the study is to examine the effect of increased SFK activity, specifically Fyn, on corneal epithelial wound healing in a mouse model of neurotrophic keratopathy.
Three mice from each following genetic background were studied: 1) wildtype (WT), 2) Fyn knockout (Fyn -/-), 3) and FynY528, a constitutively activated Fyn mouse model. After anesthetizing and disinfection, a 1.5 mm small incision lateral canthotomy was performed. Using minimal dissection and rotation of the globe, ciliary branches of the trigeminal nerve located at the posterior globe were axotomized with sharp forceps under direct observation. Antibiotic ointment was applied to the incision site and eye. Trigeminal nerve resections were performed unilaterally. After 48 hours, corneal blink was tested and mice who exhibited complete loss of corneal blink were used for corneal wounding. For wounding, a dull 1.5 mm trephine was used to demarcate the area, and the corneal epithelium was gently debrided using a 0.5mm burr. Both corneas were wounded. Antibiotic ointment was applied after debridement. Mice were serially imaged 4, 8, 16, and 24 hours after wounding and areas were analyzed using Image J.
Image analysis showed a trend towards faster wound healing in FynY528 mice compared to WT, while Fyn -/- mice exhibited slower wound healing compared to WT. Corneal epithelial wound healing rates were slower in eyes that underwent trigeminal nerve resection than those that did not.
Loss of trigeminal nerve innervation retards wound healing, suggesting a critical role for corneal nerve function in epithelial wound healing. Corneal epithelial wound healing may be augmented despite loss of corneal innervation with increased SFK activity. Results from this study suggest delayed corneal epithelial wound healing from loss of corneal innervation can be partially recovered by increasing SFK activity. Further studies to determine how SFK enhances corneal epithelial wound healing in neurotrophic keratopathy should be conducted.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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