UVR-B-induced NKR-1 Expression in Ocular Tissues is blocked by Substance P Receptor Antagonist Fosaprepitant in the Exposed as well as Unexposed Partner Eye

ABSTRACT

Purpose: To investigate the effect of NKR-1 antagonists in an established UVR-B-induced cataract mouse model. Furthermore, to examine the expression of pro-inflammatory cytokines/chemokines in mouse eyes following unilateral UVR-B exposure.

Methods: Mice received intraperitoneally injections of Fosaprepitant and Spantide I, before and after unilateral exposure to UVR-B. After day 3 and 7 post-exposure, ocular tissues were extracted for the detection of NKR-1 protein level by ELISA.

Results: Pretreatment with Fosaprepitant decreases NKR-1 expression in exposed ocular tissues as well as in the unexposed lens epithelium compared to the saline group. Spantide I treatment showed a tendency of NKR-1 overexpression in ocular tissues.

Conclusion: The clinically approved NKR-1 receptor antagonist Fosaprepitant decreases NKR-1 protein expression effectively not only in the exposed but also in the unexposed partner eye in a UVR-B irradiation mouse model. No effect was seen on the protein concentration of pro-inflammatory cytokines/chemokines in either eye.

KEYWORDS:

• Ultraviolet radiation B
• Spantide I
• Fosaprepitant (IVEMEND®)
• neurokinin receptor 1
• cytokines/chemokines

Acknowledgments

The authors thank Claudine Strack for outstanding expert help. We also thank the laboratory group for helpful discussions.

Declaration of interest

The author, Prof. Frank G. Holz, has financial support from Acucela, Allergan, Bayer, Bioeq/Formycon, CenterVue, Roche/Genentech, Heidelberg Engineering, NightStarX, Novartis, Optos, Pixium Vision and Zeiss. Furthermore, the author consults for Acucela, Apellis, Bayer, Boehringer-Ingelheim, Bioeq/Formycon, Galimedix, Roche/Genentech, Geuder, Grayburg Vision, Heidelberg Engineering, LinBioscience, Novartis, Pixium Vision, Oxurion and Stealth Bio Therapeutics. The author is also a recipient of gifts, honoraria, travel reimbursement, patent royalties, or any other financial compensation of Acucela, Allergan, Apellis, Bayer, Ellex, Roche/Genentech, Grayburg Vision, Heidelberg Engineering, LinBioscience, Novartis, Pixium Vision, Oxurion, Stealth Bio Therapeutics and Zeiss.

The other authors of this publication have no conflicts of interest to declare.

Additional information

Funding

This work was supported by the German Research Foundation “DFG” (ME 3298/4-1) (WE 1303/6-1);Deutsche Forschungsgemeinschaft [ME 3298/4-1,WE 1303/6-1].