Corneal Neurotization Rescues the Corneal Epithelium from Thinning in a Rat Model of Neurotrophic Keratopathy
Kira Antonyshyn1,2, Joseph Catapano, MD, PhD1, Jennifer Zhang, MD, PhD2, Tessa Gordon, PhD2, Gregory H. Borschel, MD, FACS, FAAP1,2.
1The University of Toronto, Toronto, ON, Canada, 2The Hospital for Sick Children, Toronto, ON, Canada.
The cornea is one of the most densely innervated tissues in the body, and in the absence of corneal sensory innervation, patients develop Neurotrophic Keratopathy (NK). NK is a disease characterized by corneal epithelial breakdown that can lead to progressive corneal scarring and ultimately, vision loss. Corneal neurotization uses nerve autografts to restore sensory innervation in the NK cornea1,2. In our rat model of NK, we previously demonstrated that corneal neurotization with common peroneal and sural nerve grafts reduces epithelial breakdown, prevents scarring, and improves the rate of epithelial healing in the cornea3. Central corneal epithelial thinning is present in corneal denervation and NK. In the present study, we evaluate the effect of corneal neurotization on corneal epithelial and stromal thickness in a rat model of NK.
METHODS: Previously validated models of NK and corneal neurotization were used in this study. The experimental groups were rats with i) NK (negative control) and ii) NK treated with corneal neurotization (treatment), and the control group consisted of rats with normally innervated corneas. In the experimental groups, NK was achieved with stereotactic ablation of the ophthalmic nerve. Four weeks after ablation, affected corneas (n=5 per group) were harvested. Three 10μm cross-sections from each cornea, sampled from representative areas of the cornea, were stained with Hematoxylin and Eosin for analysis. Each section was imaged with bright- field microscopy at 200X magnification. The epithelial and stromal thicknesses of each section were measured using ImagePro. Mean thicknesses were compared using the Kruksal-Wallis test and unpaired t-tests.
RESULTS: The central epithelial thickness of the NK corneas (15.83 ± 1.62) was significantly decreased compared to that of the central epithelium in the treated (25.07 ± 3.89, p < 0.05) and normally innervated corneas (24.75 ± 2.46, p < 0.05), the treated and normally innervated corneas not being significantly different. In contrast, the stromal thicknesses were insignificantly different in all three groups.
CONCLUSIONS: Corneal neurotization rescues the NK cornea from central epithelial thinning, suggesting the reinnervating axons of the inserted graft restore corneal epithelial integrity. We are pursuing further research with the same rat models of NK and corneal neurotization to elucidate the underlying mechanisms.
1. Elbaz U, Bains R, Zuker RM, Borschel GH, Ali A. Restoration of corneal sensation with regional nerve transfers and nerve grafts: A new approach to a difficult problem. JAMA Ophthalmol. 2014;132(11):1289-1295. doi:10.1001/jamaophthalmol.2014.2316
2. Bains RD, Elbaz U, Zuker RM, Ali A, Borschel GH. Corneal neurotization from the supratrochlear nerve with sural nerve grafts: A minimally invasive approach. Plast Reconstr Surg. 2015;135(2):397e-400e. doi:10.1097/PRS.0000000000000994
3. Catapano J, Antonyshyn K, Zhang JJ, Gordon T, Borschel GH. Corneal neurotization improves ocular surface health in a novel rat model of neurotrophic keratopathy and corneal neurotization. Investig Opthalmology Vis Sci. 2018;59(11):4345-4354.
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