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Corneal Invasion by Matrix Metalloproteinase Expressing Altered Limbal Epithelial Basal Cells

Nicholas Dushku, MD; Molykutty K. John, PhD; Gregory S. Schultz, PhD; Ted W. Reid, PhD

Arch Ophthalmol. 2001;119:695-706.

Objective  To assess the potential role of matrix metalloproteinases (MMPs) in the pathogenesis of pterygia by comparing the immunolocalization patterns of MMPs in altered limbal basal stem cells, activated fibroblasts, and areas of elastotic degeneration adjacent to the pterygia.

Methods  Nine primary and 1 recurrent pterygia along with normal superior limbal-conjunctival tissue and cornea were immunostained with mouse monoclonal antibodies specific for MMP-1, MMP-2, MMP-3, MMP-9, membrane type 1 (MT1)–MMP (MMP-14), and membrane type 2–MMP (MMP-15).

Results  Normal conjunctival, limbal, and corneal cells lacked significant immunostaining except for cell surface MT1-MMP. In contrast, altered limbal basal epithelial cells of the 9 primary and 1 recurrent pterygia immunostained for all 6 MMPs. Activated and altered fibroblasts associated with the pterygia immunostained primarily for MMP-1. In contrast, stromal areas of elastotic degeneration (pingueculae) showed variable immunostaining of MMPs.

Conclusions  Altered limbal basal epithelial cells (pterygium cells) immunostained for multiple types of MMPs in contrast to normal conjunctival, limbal, and corneal cells. The pterygium cells invading over Bowman's layer produce elevated MMP-1, MMP-2, and MMP-9 expression, which probably are the main MMPs responsible for the dissolution of Bowman's layer. Pterygium cells may also cause activation of fibroblasts at the head of the pterygium, leading to the initial cleavage of fibrillar collagen in Bowman's layer by the production of MMP-1. Altered fibroblasts in areas of elastotic degeneration (pingueculae) trailing behind the pterygium constitute a second type of tumor, which is noninvasive.

Clinical Relevance  These data of altered MMP expression support the concept that altered basal limbal epithelial cells play a key role in the formation and migration of a pterygium.

From the Department of Ophthalmology, Kaiser Permanente Medical Center, Sacramento, Calif (Dr Dushku); Department of Obstetrics and Gynecology, Institute for Wound Healing, University of Florida, Gainesville (Drs John and Schultz); and Departments of Ophthalmology and Visual Sciences, Texas Tech University, Lubbock (Dr Reid).

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