Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4345-4354. doi: 10.1167/iovs.18-24843.
Corneal neurotization is a novel surgical procedure to reinnervate the cornea in patients with neurotrophic keratopathy (NK). We developed a rat model of NK and corneal neurotization to further investigate corneal neurotization as a treatment to improve maintenance and healing of the corneal epithelium.
Thy1-GFP+ Sprague Dawley rats were used to develop the model. Corneal denervation was performed via stereotactic electrocautery of the ophthalmomaxillary branch of the trigeminal nerve. Corneal neurotization was performed by guiding donor sensory axons from the contralateral infraorbital nerve into the cornea via two nerve grafts. Corneal imaging, including nerve density measurements and retrograde labeling were performed to validate the model. In vivo assays of corneal maintenance and repair were used to examine whether treatment with corneal neurotization improved healing in rats with NK.
Corneal neurotization significantly increased corneal axon density in rats with NK (P < 0.01). Retrograde labeling of the cornea in rats with corneal neurotization labeled 206 ± 82 neurons in the contralateral trigeminal ganglion, confirming axons reinnervating the cornea derived from the contralateral infraorbital nerve. Corneal reinnervation after corneal neurotization improved corneal epithelial maintenance and corneal healing after injury (P < 0.01).
Donor nerve fibers reinnervate the insensate cornea after corneal neurotization and significantly improve corneal maintenance and repair. This model can be used to further investigate how corneal neurotization influences epithelial maintenance and repair in the context of NK.
角膜神经再支配是一种将感觉神经纤维重新支配到角膜的新型手术方法，用于治疗神经营养性角膜病变（NK）。我们建立了 NK 大鼠模型和角膜神经再支配模型，旨在进一步研究角膜神经再支配作为改善角膜上皮维持和愈合的治疗方法。
使用 Thy1-GFP+Sprague Dawley 大鼠建立模型。通过立体定向电灼三叉神经眶下支对角膜进行去神经支配。通过两根神经移植物将来自对侧眶下神经的供体感觉轴突引导至角膜，实现角膜神经再支配。进行角膜成像，包括神经密度测量和逆行标记，以验证模型。进行体内角膜维持和修复检测，以研究角膜神经再支配是否改善 NK 大鼠的角膜愈合。
角膜神经再支配显著增加 NK 大鼠的角膜轴突密度（P<0.01）。对行角膜神经再支配的大鼠进行角膜逆行标记，在对侧三叉神经节中标记了 206±82 个神经元，证实了再支配角膜的轴突来源于对侧眶下神经。角膜神经再支配后，角膜的神经再支配改善了角膜上皮的维持和损伤后的愈合（P<0.01）。
供体神经纤维在角膜神经再支配后可重新支配感觉丧失的角膜，并显著改善角膜的维持和修复。该模型可用于进一步研究角膜神经再支配如何影响 NK 情况下的上皮维持和修复。
