The role of conjunctival epithelial cells in chronic ocular allergic disease

Recent evidence suggests that mucosal epithelial cells are capable of actively participating in immune reactions via expression of surface antigens, such as adhesion molecules, and synthesis of cytokines. This appears to be important in the pathophysiology of non-ocular allergic disorders. The objectives of the experiments were to compare the expression of HLA-DR, ICAM-I and pro-allergic cytokines in conjunctival epithelial cells in the different chronic ocular allergic disorders with each other and with normal subjects. Conjunctiva from normal patients (n=10) and patients with vernal keratoconjunctivitis (VKC, n=10), atopic keratoconjunctivitis (AKC, n=10) and contact lens-associated giant papillary conjunctivitis (GPC, n=10) were examined by immunohistochemistry. Epithelial cell staining for surface antigens and cytokines was graded by one masked observer using a four point scale based on the percentage of epithelial cells staining positive. There was no expression of ICAM-1 or HLA-DR in the normal conjunctival epithelial cells, but both antigens were induced on conjunctival epithelial cells in the allergic tissue, and there was greater expression in AKC and VKC compared with GPC. Cytokines IL-6, IL-8, RANTES and TNF-alphaall localised to normal conjunctival epithelial cells. RANTES was upregulated in all the allergic disorders and IL-8 was upregulated in GPC. IL-3 and GM-CSF were not expressed in normal conjunctival epithelial cells. GM-CSF was expressed in all disorders and there was greater expression in AKC compared with GPC and VKC. IL-3 was expressed only in AKC and VKC epithelial cells. These results suggest that conjunctival epithelial cells play an important pro-inflammatory role in chronic ocular allergic diseases; ICAM-1 may allow epithelial cells to recruit, retain and locally concentrate leukocytes; the presence of HLA-DR raises the question of conjunctival epithelial cell antigen presentation. The epithelial cytokines which are upregulated are known to promote eosinophilic inflammation and are typical of allergic inflammation. The differences in cytokine patterns may be exploitable for future therapy.