Nerves, substance P and ocular surface inflammation

Abstract

AbstractCorneal nerves are instrumental to maintain cornea integrity through regulation of key physiological functions such as epithelial wound healing, tear secretion, blink reflex. Corneal nerve injury/stimulation is a common consequence of most ocular surface diseases/surgeries. Nerve disruption initiates a process named neurogenic inflammation which leads to edema, pain, and recruitment and activation of leukocytes. Interestingly, leukocyte influx in the cornea can further damage nerves by releasing inflammatory mediators‐including neuropeptides. The clinical outcome of neuroinflammation can be beneficial or detrimental to corneal integrity. On one side, it allows proper wound healing. On the other, prolonged and/or deranged neuroinflammation can permanently disrupt corneal integrity and impair vision. Substance P (SP), a peptide secreted by sensory nerves, is abundantly expressed I the cornea. SP exerts multiple biological activities, including promotion of cell migration, leukocyte activation and diapedesis, angiogenesis and pain, among others, which make it an ideal mediator of neuroinflammation in the cornea. Accumulating evidence suggests that modulation of SP activity is a promising therapeutic approach to treat signs (i.e. inflammation) and symptoms (i.e. pain) of highly prevalent diseases of the ocular surface.