Altered Expression of Fibrosis Genes in Capsules of Failed Ahmed Glaucoma Valve Implants

PURPOSE: Ahmed glaucoma valve (AGV) implant is an aqueous shunt device used to control intraocular pressure in glaucoma. Implant failure results from impervious encapsulation of the shunt plate causing increased hydraulic resistance and raised intraocular pressure. We hypothesized that deregulation of fibrosis pathway contributes to capsular resistance. We tested this by studying fibrosis related gene expression in failed AGV implants. METHODS: Differential gene expression was examined in failed AGV capsules and compared to normal control tenon. Following total RNA extraction, 84 key genes in fibrosis pathway were examined by real-time PCR using RT(2) Profiler PCR Array. Relative gene expression was calculated using ΔΔC(t) method. Gene specific TaqMan assays were used to validate select genes with ≥2 fold differential expression in the array expression profile. RESULTS: We observed differential expression in several genes in the fibrosis pathway. Almost half (39/84) of examined genes showed ≥2 fold differential expression in majority of capsules examined on the array. TaqMan assays for select genes including CCN2 (CTGF), THBS1, SERPINE1, THBS2, COL3A1, MMP3, and IL1A in an increased validation sample set showed significant changes in expression (p value from <0.001 to 0.022) at a high frequency in concurrence with our array results. CONCLUSIONS: Pathway-focused analyses identified candidate genes with altered expression providing molecular evidence for deregulation of the fibrosis pathway in AGV failure.