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N. Di Girolamo, J. Ng, M. T. Coroneo, D. Wakefield; Matrix Metalloproteinase Expression and the Effect of Ultraviolet Radiation Exposure on Ocular Surface Squamous Neoplasia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2358. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular surface squamous neoplasia (OSSN) is an uncommon tumour of the corneal/conjunctival epithelium that is thought to develop as a consequence of excessive ultraviolet (UV) radiation exposure. To date, few studies have been conducted on the molecular mechanisms of this disease. The purpose of this study was (i) to identify and localize potential mediators responsible for the development of this disease and (ii)to culture human dysplastic epithelial cells (DEC) and determine their responsiveness to UVB radiation compared to normal epithelial cells (CEC).
Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded OSSN (n=23) and normal conjunctival (n=17) tissue with antibodies to MMPs and TIMPs. Basal as well as UVB-modulated levels of MMPs and TIMPs from DEC and CEC were determined by immunoassay, zymography and RT-PCR.
A higher proportion of diseased specimens stained for MMP-1 (83%), MMP-3 (86%), TIMP-2 (87%), and TIMP-3 (83%) compared to normal conjunctiva (41%, 41%, 47%, 53% respectively). Although TIMP-1 expression seemed more abundant in normal conjunctiva (76%) compared to diseased (61%) tissue, this did not reach statistical significance. MMP-2 was evenly distributed in both groups. UVB radiation induced cell death and apoptosis at doses greater than 50 mJ/cm2 compared to 20 mJ/cm2 which caused no significant apoptosis or morphological change. Interestingly, in DECs, mRNA and protein for MMP-1 and MMP-3 were dose-dependently induced following irradiation, while the same enzymes were only up-regulated in normal CEC at doses that induced apoptosis. TIMP-1 and -2 levels remained relatively unchanged, except for a dose-dependent suppression of TIMP-3.
MMPs and TIMPs may play a significant role in the pathogenesis of OSSN and that UVB may perpetuate the development of this lesion on the ocular surface. These findings suggest UVB avoidance is prudent, both in patients with OSSN, and in the healthy population.
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