title: Substance P and its Inhibition in Ocular Inflammation.
abstract: 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.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bignami
authors.forename: Paolo
authors.initials: P
authors.lastname: Rama
authors.affiliation: Cornea and Ocular Surface Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. ferrari.giulio@hsr.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ferrari
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D018040:Receptors, Neurokinin-1; D013373:Substance P