Tissue remodeling and formation of giant papillae are some of the consequences of chronic allergic eye disorders. Remodeling involves both production and deposition of extracellular matrix (ECM) components, as well as degradation and clearance of newly synthesized products. Immunohistochemical studies have shown the increased deposition of collagens in giant papillae in VKC, possibly as a result of increased expression of growth factors,
8 which may stimulate resident fibroblasts to produce extracellular matrix proteins. The predominant collagens present in giant papillae are types I and III.
9 Both IL-4 and -13 have been reported to activate lung and skin fibroblasts to produce collagens I and III,
10 11 whereas IFN-γ may have an inhibitory effect in fibroblasts.
12 Overproduction and deposition of collagens and tissue remodeling may be modulated by matrix metalloproteinases (MMPs) and their physiological inhibitors, tissue inhibitors of metalloproteinases (TIMPs).
13 MMPs are a family of zinc- and calcium-dependent enzymes involved in many physiological and pathologic processes, including progression of tumors, metastasis, inflammatory diseases, and wound healing. Of the 17 members of the human MMP family that have been described, collagenase I (MMP-1), gelatinase A and B (MMP-2 and -9), stromelysin (MMP-3), and matrilysin (MMP-7) are those most involved in anterior segment disease and wound healing. These enzymes are produced and secreted by a variety of cells, including epithelial cells, inflammatory cells, and conjunctival fibroblasts
14 and are regulated by several cytokines, both in physiological conditions such as wound healing and in diseases states.
15 16 MMP-1 can cleave the triple helix of interstitial collagen types I, II, and III. Stromelysin and matrilysin are involved in degrading a variety of ECM components such as proteoglycans, fibronectin, and laminin. Gelatinase A and B are involved in cleaving collagen types IV (the main component of basal membrane), V, VII, and X; fibronectin; laminin; elastin; and collagen degradation products, and TIMP-1 is the natural inhibitor of both collagenase I and gelatinase.