NK1 receptor antagonists as a new treatment for corneal neovascularization.
PURPOSE
To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant.


METHODS
We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival. Clinical examination endpoints, SP levels, CNV index, and leukocyte infiltration were measured.


RESULTS
Substance P increased after injury in the corneal epithelium of both CNV models, and later in the suture model. Topical Lanepitant was nontoxic to the ocular surface and effective in reducing hemangiogenesis and lymphangiogenesis, corneal SP levels, and leukocyte infiltration, as soon as 4 days later in the alkali burn model. Topical Lanepitant, up to 7 days, was ineffective in the suture model. However, subconjunctival Lanepitant was effective in reducing lymphatic CNV, leukocyte infiltration, and SP levels in the suture model, after 10 days. Additionally, in the alkali burn model, subconjunctival Lanepitant significantly reduced blood CNV, corneal perforation rate, opacity, and leukocyte infiltration, and improved tear secretion. Finally, topical application of Befetupitant reduced CNV in the alkali burn model but was toxic owing to the vehicle (dimethyl sulfoxide [DMSO]); hence, Befetupitant was not tested in the suture model.


CONCLUSIONS
The NK1R antagonist Lanepitant is safe for the ocular surface and effective in reducing both corneal hemangiogenesis and lymphangiogenesis, and leukocyte infiltration. We suggest that inhibition of NK1R may represent an adjunctive tool in the treatment of CNV.
['Bignami|Fabio|F|', 'Giacomini|Chiara|C|', 'Lorusso|Anna|A|', 'Aramini|Andrea|A|', 'Rama|Paolo|P|', 'Ferrari|Giulio|G|']
D000287:Administration, Topical D000818:Animals D002057:Burns, Chemical D003228:Conjunctiva D003315:Cornea D065306:Corneal Injuries D016510:Corneal Neovascularization D004195:Disease Models, Animal D005126:Eye Burns D005260:Female D005500:Follow-Up Studies D007150:Immunohistochemistry D007211:Indoles D007267:Injections D051379:Mice D008810:Mice, Inbred C57BL D064729:Neurokinin-1 Receptor Antagonists D009883:Ophthalmic Solutions D010880:Piperidines D011725:Pyridines D018040:Receptors, Neurokinin-1 D013537:Sutures D041623:Tomography, Optical Coherence D016896:Treatment Outcome
NK1 receptor corneal neovascularization Substance P Lanepitant neuropeptide