Differential Effects of Two Ocular Surface Injury Models on the Functional Properties of Regenerated Corneal Sensory Nerves

Abstract

Purpose : Dysfunction of corneal sensory nerves can manifest in a wide range of sensory alterations, spanning from insufficient sensation as found in neurotrophic keratopathy to dysesthesia observed in Dry Eye Disease, an ocular surface disorder estimated to affect 5% of the global population. Changes in corneal sensory nerve function after recovery from injury are not well understood. This study tested the hypothesis that corneal sensory nerves regenerated from ocular surface injury display alterations in their activity profiles.

Methods : The impact of regeneration from injury on corneal nerve properties was tested using two models of nerve injury—Corneal Epithelial Debridement (CED) and Benzalkonium chloride (BAK) chemical injury, in adult Sprague Dawley rats of both sexes. CED is one of the most common corneal injury models and was induced using a rotary burr tool, with the entire corneal epithelium removed while sparing the corneal limbus. BAK injury was administered as a prolonged (30min+) ocular instillation with 0.01% Benzalkonium chloride, a common preservative found in eye drops that can damage corneal epithelium and nerves. At 14 and 28 days post injury, corneal nerve functional profiles were assessed in anesthetized rats using in vivo electrophysiological recordings of the trigeminal ganglion, which houses the cell bodies of corneal nerves, while the cornea was exposed to a range of stimuli that activate ion channels responsible for corneal nerve sensation.

Results : Our preliminary data indicate that the two injury models lead to differential response profiles of regenerated nerves that can be observed at both 14 and 28 days post injury. Compared to injury-naïve rats (n=25), CED animals (n=10) showed signs of decreased responsiveness, with blunted responses to stimuli like ocular dryness, hyperosmolar stress, and temperature decreases of the ocular surface. Conversely, BAK-treated animals (n=13) displayed activity shifts toward increased responsiveness compared to injury-naive animals, with augmented responsiveness to cooling and heating of the ocular surface.

Conclusions : Our findings suggest that corneal sensory nerves that regenerate from injury show long-lasting and differential alterations in their functional activity profiles that are dependent on the model used for ocular surface injury.

This is a 2021 ARVO Annual Meeting abstract.