Topical cis-urocanic acid prevents ocular surface irritation in both IgE -independent and -mediated rat model

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 255; no. 12; pp. 2357 - 2362
• Main Authors: Jauhonen, Hanna-Mari, Laihia, Jarmo, Oksala, Olli, Viiri, Johanna, Sironen, Reijo, Alajuuma, Päivi, Kaarniranta, Kai, Leino, Lasse
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2017; Springer Nature B.V
• Subjects: Administration, Topical; Allergies; Animal models; Animals; Antibodies, Anti-Idiotypic - immunology; Apoptosis; Basic Science; Blue stain; Caspase; Caspase-3; Compound 48/80; Conjunctiva; Conjunctivitis; Conjunctivitis, Allergic - chemically induced; Conjunctivitis, Allergic - immunology; Conjunctivitis, Allergic - prevention & control; Dexamethasone; Disease Models, Animal; Epithelial cells; Eye; Hay fever; Hyperemia; Immunoglobulin E; Immunoglobulin E - immunology; Irritation; Leakage; Medicine; Medicine & Public Health; Oleic Acids - administration & dosage; Olopatadine; Ophthalmic Solutions; Ophthalmology; Ovalbumin; p-Methoxy-N-methylphenethylamine - toxicity; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rodents; Statistical analysis; Allergic conjunctivitis; Ocular allergy; Experimental animal model; Cis-urocanic acid
• ISSN: 0721-832X; 1435-702X
• DOI: 10.1007/s00417-017-3781-z

Purpose Our purpose was to investigate the effect of locally administered cis-urocanic (cis-UCA) in two experimental models of allergic conjunctivitis. Methods The compound 48/80 (C48/80)-induced ocular irritation model (IgE-independent) and the ovalbumin (OA)-induced ocular allergy model (IgE-mediated) were used to test and compare the effect of cis-UCA on dexamethasone, ketotifen and olopatadine. In the C48/80 model, clinical severity scoring from photographs, immunohistochemical analysis of nuclear Ki-67 antigen to quantify actively proliferating epithelial cells and of caspase-3 enzyme to identify apoptotic activity in the conjunctival tissue were used. In the OA model, an Evans Blue stain concentration of conjunctival tissue was used to evaluate vascular leakage due to allergic reaction. Results The cis-UCA was well tolerated and effective in both the IgE-independent and -mediated rat models. Treatment with C48/80 caused conjunctival hyperaemia, which was significantly inhibited by ketotifen at the 6 h time point ( p  = 0.014) and by dexamethasone and cis-UCA 0.5% at 12 ( p  = 0.004) and 24 ( p  = 0.004) hour time points. In a comparison between the active drug treatments, only ketotifen showed a significant difference ( p  = 0.023) to cis-UCA treatment at the 1 h time point, otherwise there were no statistically significant differences between the active drugs. Ketotifen, dexamethasone and cis-UCA 0.5% significantly inhibited the C48/80-induced nuclear accumulation of Ki-67, without differences between the active treatment groups. In the OA model, cis-UCA 0.5% did not inhibit the vascular leakage of conjunctiva, whereas cis-UCA 2.5% of was at least equally effective compared to olopatadine, abolishing the allergic vascular leakage response almost completely. Conclusions The present findings in the two AC models suggest that cis-UCA might have anti-allergic potency both in immediate and delayed-type allergic reactions in the eye.