Corneal nerves are instrumental to maintain cornea integrity through regulation of key physiological functions such as tear secretion, blink reflex, and
neuropeptide turnover. Corneal nerve injury/stimulation can follow many insults including mechanical/chemical
trauma,
infections and 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 ensures prompt wound healing and prevents
infections. On the other, prolonged and/or deranged
neuroinflammation can permanently disrupt corneal integrity and impair vision. The cornea is an ideal site to study peripheral
neuroinflammation and
neurogenic inflammation since it receives the highest density of sensory nerves of the entire body. We will review the corneal nerve anatomy and neurochemistry, discuss the beneficial and detrimental effects of
neurogenic inflammation in corneal wound healing, inflammatory processes, and
pain. We will also examine the emerging remote impact of corneal nerve disruption on the trigeminal ganglion and the brain, highlighting the key role of
neuropeptide Substance P. Finally, we will discuss the clinical relevance of such neuroinflammatory network in the context of severe and highly prevalent ocular diseases, including potential treatments.