Di Girolamo N, Wakefield D, Coroneo M T
Inflammation Research Unit, School of Pathology, University of New South Wales, Australia.
Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4142-9.
Pterygia are a proliferative and inflammatory growth of limbal epithelial stem cell origin, characterized by corneal tissue invasion and extensive matrix remodeling including the destruction of Bowman's layer (BL). The purpose of this study was to determine the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) at the advancing pterygium edge.
Formalin-fixed, paraffin-embedded whole eyes (n = 11) with pterygia attached, were serially sectioned and analyzed immunohistochemically to determine the spatial distribution of four MMPs and three TIMPs. Tear samples were collected from other patients with pterygia (n = 11) and displayed by gelatin zymography.
Collagenase-1 was expressed by pterygium epithelial cells, corneal stromal fibroblasts and pterygium fibroblasts that had migrated between the epithelium and BL at the advancing pterygium edge. Collagenase-3 and gelatinases A and B were detected in all pterygia, intensely staining columnar epithelial cells directly adjacent to the denatured BL. In addition, gelatinase A immunoreactivity was observed on BL. Immunoreactivity for TIMP-1 and -3 paralleled that of the gelatinases, with more intense staining in epithelial cells and fibroblasts where BL was absent. TIMP-2 was faintly detected 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 contralateral control eyes.
This investigation is the first to identify the expression pattern of MMPs and TIMPs at the advancing pterygium edge in specimens of human 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 pathogenesis of pterygia.
翼状胬肉是一种源于角膜缘上皮干细胞的增殖性和炎症性生长物，其特征为角膜组织侵袭和广泛的基质重塑，包括Bowman层（BL）的破坏。本研究的目的是确定基质金属蛋白酶（MMPs）和MMP组织抑制剂（TIMPs）在进展期翼状胬肉边缘的表达情况。
对11只附有翼状胬肉的福尔马林固定、石蜡包埋的全眼球进行连续切片，并进行免疫组织化学分析，以确定四种MMPs和三种TIMPs的空间分布。从其他翼状胬肉患者（n = 11）收集泪液样本，并通过明胶酶谱法进行分析。
胶原酶-1在翼状胬肉上皮细胞、角膜基质成纤维细胞以及在进展期翼状胬肉边缘上皮与BL之间迁移的翼状胬肉成纤维细胞中表达。在所有翼状胬肉中均检测到胶原酶-3、明胶酶A和B，紧邻变性BL的柱状上皮细胞呈强烈染色。此外，在BL上观察到明胶酶A免疫反应性。TIMP-1和-3的免疫反应性与明胶酶平行，在无BL的上皮细胞和成纤维细胞中染色更强。TIMP-2在翼状胬肉上皮细胞中微弱检测到，但在翼状胬肉成纤维细胞中染色强烈。明胶酶B是泪液中含量最丰富的明胶分解酶，与对侧对照眼相比，翼状胬肉患者眼中其水平升高约两倍。
本研究首次确定了人眼标本及翼状胬肉患者泪液中进展期翼状胬肉边缘MMPs和TIMPs的表达模式。这些酶可能是导致BL破坏的原因，其差异表达模式表明每种酶可能在翼状胬肉的发病机制中发挥选择性作用。
