Abstract
Abstract: :
Purpose: Ocular Cicatricial Pemphigoid (OCP) is an autoimmune disorder characterized by conjunctival inflammation and progressive fibrosis. Gene expression profiling was conducted on conjunctiva from a patient with biopsy proven OCP and from a normal individual, using oligonucleotide microarray analysis to examine the differential gene expression profile of conjunctiva affected by OCP. Methods: Total RNA was extracted from biopsies of conjunctiva of an untreated patient with OCP and a control subject. mRNA was amplified with the T7 amplification method, DNA synthesized, labelled and successfully hybridized onto cDNA microarray of 10,000 genes. Results: 256 (2.56%) of genes were differentially expressed in the OCP conjunctiva; forty-six genes were found up-regulated and 210 genes were down-regulated. The up-regulated genes included Tripeptidyl Peptidase II and extracellular matrix (ECM) modeling enzymes [Plasminogen Activator Inhibitor II (PAI-II), Tissue Inhibitor of Matrix Metalloproteinase 2 (TIMP-2)]; epithelial cell adhesion molecules [Keratin 14, 5, Bullous Pemphigoid Antigen 1 (BP 230), etc], as well as other ECM modeling enzymes [Urokinase-type Plasminogen Activator (u-PA), Matrix Metalloproteinase 14 (MMP-14), etc] were down-regulated. The expression pattern of the genes suggests a diminished expression of molecules involved in the attachment of epithelium to the basement membrane and a relatively decreased Plasmin-MMP system, which in turn may promote excessive accumulation of matrix proteins during conjunctival scarring. Conclusions: We report here the first global profile of conjunctiva gene expression in OCP, suggesting the potential role of molecules known to be important for epithelial cell attachment and for synthesis and degradation of extracellular matrix, as well as certain molecules that have not been previously implicated in the pathogenesis of OCP. The information could serve as a basis for further study to enhance our understanding about molecular mechanisms of disease process.
Keywords: conjunctiva • gene microarray • autoimmune disease