Neuropeptides, and specifically Substance P (SP), can crucially contribute to the ocular inflammatory
response. SP is an undecapeptide that is secreted from sensory nerve endings and from
various immune cells during inflammation. SP modulates ocular inflammation through its binding
with the high-affinity neurokinin-1 receptor (NK-1R). This receptor is expressed on nerves, immune
cells, and epithelial cells.
SP is a key mediator of neurogenic inflammation as it induces increased microvascular permeability,
vasodilatation, plasma extravasation, and subsequent tissue edema. In addition, macrophages can release
inflammatory mediators such as interleukins, chemokines, and growth factors in response to SP stimulation.
Inhibition of SP activity, either through blockade of the neuropeptide release or the use of SP receptor antagonists, ameliorates
ocular inflammation, it restores immune privilege and improves a number of clinical endpoints associated with
inflammation, such as corneal opacity, ocular perforation, and angiogenesis.
This review of the literature will summarize the role of SP in the ocular inflammatory response (with an emphasis on the
ocular surface). In addition, it will review the therapeutic effects of SP blockade to control ocular inflammation (i) in animal
models and (ii) in highly prevalent human diseases.