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L. Motterle, P. Brun, M. Bortolotti, F. Piliego, A. Di Stefano, A. Leonardi; Expression of Histamine Receptors in Vernal Keratoconjunctivitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1927.
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© ARVO (1962-2015); The Authors (2016-present)
Histamine receptor (HR)-1 antagonists have been shown to be of limited use in the treatment of chronic diseases such as vernal keratoconjunctivitis (VKC). The recently described HR4 has been linked to the pathology of allergy. The aim of this study was to evaluate HR expression in conjunctival tissues from normal subjects and from VKC patients, and in conjunctival cell cultures.
Conjunctival biopsies were obtained from healthy donors (N=6) and from tarsal conjunctiva of VKC patients (N=9). HR1 variant (v)1, HR1-v3, HR2-v1, HR2-v2, HR3 and HR4 mRNA were detected by RT-PCR. HR expression was also determined in conjunctival fibroblast cultures exposed for 24 hours to 10 ng/ml of histamine, IL-4, and TNF-α. Correlations between HR expression and clinical parameters were also investigated.
Normal human conjunctiva expressed both variants of HR1 and to a lesser degree, HR2-v3 and H4R. HR2-v1 and HR3 were faintly expressed. All HR were over-expressed in all VKC samples. HR1-v1, HR1-v3 and HR2-v2 were highly expressed in VKC compared to normal tissues (p<0.05). HR2-v1 was slightly expressed but significantly increased compared to controls (p=0.02). Interestingly, HR4 expression in VKC was 5 times more expressed than normal tissues (p=0.008). Although HR3 was 3 times more expressed in VKC compared to normal tissues, its expression was not statistically significantly increased. In cell cultures, HR2 expression was increased 8 times by IL-4 and 3 times by histamine compared to controls. HR4 was increased 3 times by IL-4 compared to controls.
HR1 and HR2 are normally expressed in human conjunctiva. Increased expression of all HR in VKC indicate a relevant role of histamine and its receptors in the pathogenesis of VKC. Since HR4 has been related to Th2 and eosinophil activation, its increased expression in VKC indicate that HR4 may be a future target in the treatment of severe ocular allergic inflammation.
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