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Originally published In Press as doi:10.1167/iovs.08-3147 on May 6, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:4588-4596.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-3147
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Increased Expression of Gelatinase (MMP-2 and MMP-9) in Pterygia and Pterygium Fibroblasts with Disease Progression and Activation of Protein Kinase C

Shun-Fa Yang,1,2 Ching-Yang Lin,3 Pei-Yu Yang,4 Shih-Chun Chao,3 Yi-Zhen Ye,4 and Dan-Ning Hu4,5

1From the Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 3Department of Ophthalmology and 4Cell Culture Laboratory, Department of Medical Research, Show Chwan Memorial Hospital, Changhua, Taiwan; and 5Tissue Culture Center, New York Eye and Ear Infirmary, New York, New York.

PURPOSE. To study the expression of matrix metalloprotease (MMP)-2 and MMP-9 mRNA and activities in various stages of surgically excised pterygium specimens and cultured pterygium fibroblasts and to study the effects of activation of protein kinase C (PKC) on the expression of these MMPs in pterygium fibroblasts.

METHODS. MMP-2 and MMP-9 mRNA expression and activities in 15 pterygium tissues and cultured pterygium fibroblasts were measured by RT-PCR and zymography. Five normal conjunctiva specimens and fibroblasts were tested as the controls. Changes of expression of MMP-2 and MMP-9 of fibroblasts after the simulation of a standard PKC activator, 2-O-tetradecanoyl-phorbol-13-acetate (TPA), were studied.

RESULTS. MMP-2 and MMP-9 expression in pterygium tissues and fibroblasts was greater than those of normal tissues and fibroblasts and was closely relevant to the progression of pterygium. In early-stage pterygium tissues and cultured fibroblasts, MMP-9 was not expressed, activated MMP-2 could not be detected, and only a small amount of latent MMP-2 was present. In advanced-stage pterygium (pterygium head passed the papillary region), MMP-9 was expressed; activated MMP-2 and a large amount of latent MMP-2 could be detected in pterygium tissues and fibroblasts. TPA stimulated the expression of MMP-2 and MMP-9 by pterygium fibroblasts isolated from early-stage specimens in a dose-dependent manner.

CONCLUSIONS. MMP-2 and MMP-9 expression by pterygium fibroblasts is significantly increased after the progression of pterygium. Activation of the PKC signaling pathway, aside from other previously reported signaling pathways, may play a role in the development and progression of pterygium.






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