Corneal Neurotization Improves Ocular Surface Health in a Novel Rat Model of Neurotrophic Keratopathy and Corneal Neurotization

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4345-4354. doi: 10.1167/iovs.18-24843.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cornea / innervation*
  • Corneal Dystrophies, Hereditary / physiopathology
  • Corneal Dystrophies, Hereditary / surgery*
  • Denervation
  • Disease Models, Animal*
  • Male
  • Nerve Regeneration / physiology*
  • Nerve Transfer*
  • Rats
  • Rats, Sprague-Dawley
  • Trigeminal Nerve / physiology*
  • Trigeminal Nerve Diseases / physiopathology
  • Trigeminal Nerve Diseases / surgery*

Grants and funding