Georgakarakos, ND; (2014) Epithelial remodelling of the conjunctiva in ocular allergy. Doctoral thesis , UCL (University College London).

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Abstract

Background: The spectrum of ocular allergy includes reversible conditions (seasonal, perennial and giant papillary conjunctivitis) and irreversible chronic severe forms of disease involving the cornea (vernal and atopic keratoconjunctivitis). Conjunctival remodelling may play a role in the pathogenesis of chronic allergic eye disease (CAED). Based on findings on asthmatic airway epithelia, it is suggested in chronic asthma that activation of the epithelial-mesenchymal trophic unit (EMTU hypothesis) and EGFR may participate in disease development and account for chronicity, severity and poor response to steroid treatment. This thesis investigates the potential application of the EMTU hypothesis to CAED. Aims and Methods: Conjunctival biopsies of healthy subjects, SAC, GPC (controls group) were compared to VKC and AKC (CAED group) and conjunctival tissues of active and treated OCP. Expression of EGFR, TGFa and CD44 was assessed by means of immunohistochemistry. Cells of two human epithelial conjunctival cell lines (IOBA-NHC & CHwK) received single and multiple cytokine treatments (PMA, IL-17A, TNFQ/IL-1β) and secretion of EGFR, VEGF, CD44, TGFa and p21waf of harvested supernatants were assessed by means of ELISA. Statistical analysis was performed using Mann-Whitney test for the immunohistochemistry and t-test for the ELISA results. Results: Immunohistochemistry studies revealed that there was increased expression of all EMTU remodelling markers in the CAED group compared to Controls (p<0.01). OCP conjunctival biopsies showed no expression for EGFR and TGFa. There was increased secretion of the remodelling molecules by both cell lines after single/multiple cytokine treatments. Conclusions: Epithelial conjunctival remodelling may be responsible for disease severity in CAED as shown in chronic asthma. Epithelial cell EGFR-mediated remodelling parallels the observations made in chronic asthmatic epithelia and the results are in agreement with previous studies in biopsies and tears of VKC patients. Finally suggestions for new treatment strategies are proposed to prevent or inhibit disease perpetuation.

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