Conjunctival expression of matrix metalloproteinase and proinflammatory cytokine genes after trichiasis surgery.

Abstract

PURPOSE. Trachoma, the leading infectious cause of blindness, is a chronic inflammatory scarring condition. Blindness follows the development of trichiasis, which is treated surgically. Unfortunately, it frequently recurs, compromising the treatment. In this study, gene expression analysis was used to examine factors that may be involved in the inflammation and tissue remodeling after surgery. METHODS. Subjects were examined before and at 1 and 4 years after surgery. Conjunctival swab samples were collected for bacterial culture, Chlamydia trachomatis PCR, and RNA isolation at 1 year. Quantitative real-time PCR was performed to measure the expression of tumor necrosis factor-alpha (TNF), interleukin-1beta (IL1B), matrix metalloproteinase-1 (MMP1), MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), TIMP-2, and hypoxanthine phosphoribosyl transferase-1 (HPRT1). RESULTS. Two hundred forty individuals with trachomatous trichiasis were recruited. One year after surgery, recurrent trichiasis was associated with a reduced MMP-1/TIMP-1 ratio (P = 0.029). IL1B expression was elevated in the presence of either conjunctival bacterial infection (P = 0.011) or inflammation (P = 0.002). TNF expression was greater in the Mandinka ethnic group (P < 0.0001), and it was increased when clinical inflammation was associated with nonchlamydial bacterial infection (P = 0.012). MMP-9 expression increased when conjunctival inflammation was associated with bacterial infection (P = 0.007). CONCLUSIONS. Recurrent trichiasis was associated with a reduced MMP-1 to TIMP-1 ratio, which may favor the accumulation of fibrotic tissue. Nonchlamydial bacterial infection may induce factors that contribute to conjunctival tissue remodeling and recurrent trichiasis in trachoma. Prospective studies are needed to assess the potential importance of these and other factors in progressive disease.