Olopatadine ophthalmic solution suppresses substance P release in the conjunctivitis models

Abstract

Background: Olopatadine hydrochloride ophthalmic solutions are treated for allergic conjunctival diseases that are a selective histamine H1 receptor antagonist and an inhibitor of the release of mediators including histamine from the human mast cells. Substance P (SP) levels are increased in tears of patients with allergic conjunctivitis. However, little is known about the regulation of SP release by anti-allergic ophthalmic solutions.

Objective: We investigated that the effect of olopatadine hydrochloride ophthalmic solutions (olopatadine 0.1% and olopatadine 0.2%) on rat conjunctivitis models compared with other anti-allergic ophthalmic solutions.

Methods: Conjunctivitis was induced by subconjunctival injection of histamine or intravenous injection of ovalbumin in rats passively sensitized with anti-ovalbumin anti-serum. The releases of SP were determined in the conjunctiva and tears using rat antigen-induced conjunctivitis models.

Results: Olopatadine 0.1% and 0.2% significantly inhibited the increased conjunctival dye leaked in the histamine- or antigen-induced hyperpermeability. The inhibitory effects by olopatadine were more potent than by other tested anti-allergic ophthalmic solutions. Moreover, olopatadine significantly inhibited the release of SP from the conjunctiva.

Conclusion: These results indicate that olopatadine ophthalmic solutions appear to exert additional SP release inhibition besides dual-action such as selective histamine H1 receptor antagonistic action and mast cell stabilization action.

Keywords: Allergic conjunctivitis; Olopatadine hydrochloride; Ophthalmic solution; Rat; Substance P.

Fig. 1

Effects of olopatadine ophthalmic solution 0.1% and 0.2% compared other anti-allergic ophthalmic solutions on histamine (A) or ovalbumin (B)-induced conjunctival vascular hyperpermeability in passively sensitized rats. Olopatadine 0.1%, olopatadine 0.2%, levocabastine 0.025%, and tranilast 0.5% were applied topically onto the eye 30 min before the challenge of antigen and histamine with Evans blue dye. Each column and vertical bar represents the mean ± SE of 8-11 rats. ^**p < 0.01, ^***p < 0.001: significantly different from the control group (Student's t-test). ^###p < 0.001: significantly different from the control group (Aspin Welch test).

Fig. 2

Effects of olopatadine ophthalmic solution 0.1% and 0.2% on ovalbumin-induced conjunctival vascular hyperpermeability in passively sensitized rats. Olopatadine ophthalmic solution 0.1% (olopatadine 0.1%), olopatadine ophthalmic solution 0.2% (olopatadine 0.2%) were applied topically onto the eyes 24 h, 6 h prior to the challenge of antigen, and 5 min after the challenge of antigen. Each column and vertical bar represents the mean ± SE of 4-7 rats. ^***p < 0.001: significantly different from the control group (Student's t-test). ^###p < 0.001: significantly different from the control group (Aspin Welch test).

Fig. 3

Effects of olopatadine ophthalmic solution compared other anti-allergic ophthalmic solution on substance P (SP) contents (A) and SP release (B) in conjunctiva induced by ovalbumin in passively sensitized rats. SP contents were measured 30 min after antigen challenge. Ophthalmic solutions were instilled at 30 min before antigen challenge and immediately after antigen challenge into the bilateral eye with 10 µL/site. Each column and vertical bar of SP contents (A) represents the mean ± SE of 7-9 rats. ^*p < 0.05, ^**p < 0.01: significantly different from the control group (Student's t-test). ^††p < 0.01: significantly different from the pre group (Student's t-test).

Fig. 4

Effects of olopatadine ophthalmic solution and other anti-allergic ophthalmic solutions on substance P (SP) contents in tears induced by ovalbumin in passively sensitized rats. SP contents were measured 30 min after antigen challenge. Ophthalmic solutions were instilled at 30 min before antigen challenge and immediately after antigen challenge into the bilateral eye at 10 µL/site. Each column and vertical bar represents the mean ± SE of 5-7 rats. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001: significantly different from the control group (Student's t-test). ^†p < 0.05: significantly different from the olopatadine 0.1% group (Student's t-test).