Mechanistic Variability in Corneal Nerve Recovery Linked to Injury Type

The cornea, a transparent tissue covering the eye, is essential for clear vision and represents the most densely innervated tissue in the body. Its extensive sensory innervation provides both sensory perception and crucial trophic support, maintaining corneal health and integrity. Disruption of corneal innervation leads to neurotrophic keratitis (NK), a pathological condition caused by ocular injury, surgical procedures, or underlying diseases. The limited understanding of NKs pathophysiological mechanisms has hindered the development of innovative therapeutic approaches. In this study, we comparatively analyzed corneal innervation morphogenesis and regeneration across two clinically relevant injury models, highlighting both commonalities and differences among these contexts. Our results demonstrate that corneal nerve morphogenesis and maturation span approximately 13 weeks, from embryonic day 12 (E12) through three months of age. Additionally, we observed that the specification of distinct nerve fiber types coincided temporally with a significant enhancement in corneal sensitivity. Furthermore, we found that the type of innervation loss--either via axotomy or abrasion--differentially affected corneal sensitivity and epithelial cell homeostasis. Importantly, the regeneration mechanisms following injury were also distinctly dependent on the type of nerve damage sustained. Collectively, these findings underscore both the shared characteristics and unique aspects inherent in each NK model, highlighting the necessity for tailored therapeutic strategies specific to individual patterns of corneal innervation disruption.