Differential expression of matrix metalloproteinases and their tissue inhibitors at the advancing pterygium head

PURPOSE. Pterygia are a proliferative and inflammatory growth of limbal epi thelial stem cell origin, characterized by corneal tissue invasion and exte nsive matrix remodeling including the destruction of Bowman's layer (BL). T he purpose of this study was to determine the expression of matrix metallop roteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) at the advancing pt erygium edge. METHODS. Formalin-fixed, paraffin-embedded whole eyes (n = 11) with pterygi a attached, were serially sectioned and analyzed immunohistochemically to d etermine the spatial distribution of four MMPs and three TIMPs. Tear sample s were collected from other patients with pterygia (n = 11) and displayed b y gelatin zymography. RESULTS. Collagenase-1 was expressed by pterygium epithelial cells, corneal stromal fibroblasts and pterygium fibroblasts that had migrated between th e epithelium and BL at the advancing pterygium edge. Collagenase-3 and gela tinases A and B were detected in all pterygia, intensely staining columnar epithelial cells directly adjacent to the denatured BL. In addition, gelati nase A immunoreactivity was observed on BL. Immunoreactivity for TIMP-1 and -3 paralleled that of the gelatinases, with more intense staining in epith elial cells and fibroblasts where BL was absent. TIMP-2 was faintly detecte d in pterygium epithelial cells but intensely stained pterygium fibroblasts . Gelatinase B was the most abundant gelatinolytic enzyme present in tears, elevated approximately twofold in eyes with pterygia versus the contralate ral control eyes. CONCLUSIONS. This investigation is the first to identify the expression pat tern of MMPs and TIMPs at the advancing pterygium edge in specimens of huma n eyes and in tears derived from patients with pterygia. These enzymes may be responsible for the destruction of BL, and their pattern of differential expression suggests that each may play a selective role in the pathogenesi s of pterygia.