Neurotrophin-4 as a promising therapy for corneal injuries: Enhancing epithelial repair and nerve regeneration in abrasion and alkali burn models

Corneal injury and nerve degeneration are complex issues associated with various eye diseases, presenting significant challenges in the field of ophthalmology. Current treatment methods often fail to completely restore corneal nerve function and tissue integrity after injury, underscoring the urgent need for new regenerative strategies. Neurotrophin-4 (NT-4), a member of the neurotrophin family, exerts crucial roles in cell survival and tissue repair through binding to the TrkB receptor. This study investigates the therapeutic potential of NT-4 for corneal injury. In vitro experiments demonstrated that NT-4 enhanced the migration of corneal epithelial cells and axonal outgrowth of trigeminal ganglion cells, effects that were abrogated by the TrkB-specific inhibitor ANA-12. In mouse models, compared to control groups, NT-4 accelerated the healing of both corneal abrasions and alkali burns, elevated corneal nerve density, restored corneal transparency. These findings suggest that NT-4 plays a pivotal role in corneal epithelial repair and sensory nerve regeneration through TrkB-mediated mechanisms, supporting its potential as a therapeutic agent for managing ocular surface injuries.