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Substance P receptor antagonists fosaprepitant and spantide in an UVR‐B‐induced cataract mouse model
Author(s) -
Wegener Alfred,
Kronschläger Martin,
Schönfeld CarlLudwig,
Holz Frank,
Meyer Linda,
Gross Janine
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.5359
Subject(s) - cornea , saline , chemokine , corneal epithelium , medicine , ciliary body , receptor , pathology , endocrinology , ophthalmology
Purpose To investigate the neurokinin receptor‐1 (NKR‐1) antagonists fosaprepitant and spantide in an UVR‐B‐induced cataract mouse model. To examine their effect on the expression of pro‐inflammatory cytokines and chemokines in ocular tissues of both eyes after unilateral UVR‐B exposure. Methods Mice were injected intraperitoneally with NKR‐1 antagonists before and after unilateral UVR‐B exposure to a 5‐fold cataract threshold dose. The contralateral partner eye was completely shielded during the experiment. Control mice were similarly injected with saline only. Mice were categorized into latency period groups of 3 and 7 days following exposure. Subsequently, eyes were enucleated and ocular tissues were microsurgically dissected for NKR‐1 protein concentration by enzyme‐linked immunosorbent assay (ELISA). Cytokines and chemokines in ocular tissue samples were measured using a Multiplex Immunoassay. Results Pretreatment with fosaprepitant decreases NKR‐1 protein levels in mouse eyes after UVR‐B exposure to only one eye. NKR‐1 protein level was reduced in the exposed cornea, lens epithelium, iris/ciliary body, aqueous humor, retina and choroid as well as in the unexposed lens epithelium when compared with the saline treated mice. Spantide I treatment showed nearly the same NKR‐1 level in comparison to the saline group. Initiated fosaprepitant injection resulted in a significant reduction of Gro‐alpha/CXCL1 in the exposed cornea. No differences were measured between the treatment groups of other tested cytokines/chemokines in the mouse eye. Conclusion The UVR‐B induced expression of NKR‐1 in ocular tissues is decreased by fosaprepitant in the exposed as well as in the unexposed partner eye. A previously reported sympathizing NKR‐1 upregulation in the unexposed partner eye can be counteracted by fosaprepitant. Therefore, substance P and its receptor seem to be the signaling molecules involved in the contralateral reaction following unilateral UVR‐B exposure.