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This Article Full Text Full Text (PDF) Supplementary Figures All Versions of this Article: iovs.08-1988v1 49/12/5295    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ng, J. Articles by Di Girolamo, N. Search for Related Content PubMed PubMed Citation Articles by Ng, J. Articles by Di Girolamo, N.

Ultraviolet Radiation and the Role of Matrix Metalloproteinases in the Pathogenesis of Ocular Surface Squamous Neoplasia

¹From the Inflammatory Diseases Research Unit, School of Medical Sciences, The University of New South Wales, Sydney, Australia; and the ²Department of Ophthalmology, Prince of Wales Hospital, Sydney, Australia.

PURPOSE. Ocular surface squamous neoplasia (OSSN) is an uncommon tumor of the corneal and conjunctival epithelium associated with risk of permanent visual impairment. The purposes of this study were to (1) identify and localize potential mediators in tissue from patients with OSSN and (2) culture human dysplastic conjunctival epithelial cells (DCECs) to determine their responsiveness to ultraviolet (UV)-B radiation compared with normal conjunctival epithelial cells (NCECs).

METHODS. Immunohistochemical analysis was performed on OSSN (n = 23) and normal conjunctival (n = 17) tissue to identify matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Cell viability as well as basal and UVB-modulated levels of MMPs and TIMPs from DCECs and NCECs was determined by immunoassays, zymography, and RT-PCR.

RESULTS. A higher proportion of diseased specimens stained for MMP-1 (83%), MMP-3 (86%), TIMP-2 (87%), and TIMP-3 (83%) compared with normal conjunctiva (41%, 41%, 47%, and 53%, respectively). UVB radiation induced cell death and apoptosis at doses 50 mJ/cm². MMP-1 and -3 mRNA and protein expression in DCECs was induced by UV and was mitogen-activated protein kinase–dependent, although the same enzymes were upregulated in NCECs only at doses that induced apoptosis. TIMP-1 and -2 levels remained relatively unchanged, except for a dose-dependent suppression of TIMP-3.

CONCLUSIONS. The results suggest that MMPs and TIMPs play a significant role in the pathogenesis of OSSN and that UVB initiates and perpetuates the development of this lesion on the ocular surface.