Growth factors and collagen distribution in vernal keratoconjunctivitis

PURPOSE: To study the extracellular composition of giant papillae in vernal keratoconjunctivitis (VKC) and the expression of growth factors that may stimulate fibrosis. METHODS: Upper conjunctival specimens were obtained by biopsy in 9 patients affected by active tarsal VKC (14 eyes) and 10 normal control subjects. Immunohistochemistry was performed on tissue sections using monoclonal antibodies (mAbs) for collagens I, III, and VII; tumor necrosis factor (TNF)-alpha; transforming growth factor (TGF)-ss1; basic fibroblast growth factor (bFGF); and platelet-derived growth factor (PDGF). The mAbs anti-tryptase, anti-CD4, anti-CD68, and anti-EG2 were used as markers for mast cells, T-helper lymphocytes, macrophages, and eosinophils, respectively. Immunofluorescent double-staining for growth factors and cell markers was performed in VKC tissues. RESULTS: Immunostaining was highly positive for collagens I, III, and VII in the subepithelium of VKC conjunctiva. Image analysis showed a significant increase of staining per tissue area for both collagens I and VII and increased basal membrane length. The number of cells positive for TNF-alpha, TGF-ss, bFGF, or PDGF was significantly higher in VKC tissue than in control samples. Double staining showed that eosinophils and macrophages were the main sources of PDGF and that FGF was expressed by 46% of mast cells. Significant PDGF and FGF staining was observed in the conjunctival epithelium and vascular endothelium of all VKC tissues. CONCLUSIONS: In giant papillae of VKC, the extracellular matrix is characterized by overproduction of collagens. Expression of growth factors in the conjunctiva by resident cells (mast cells, epithelial cells, endothelial cells) and inflammatory cells (macrophages, eosinophils) may contribute to papillae formation and fibrosis evolution in chronic ocular allergic diseases.