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Alka Mahale, Maha W Othman, Sami Al Shahwan, Ibrahim Al Jadaan, Ohoud A Owaidhah, Deepak Edward; Altered expression of fibrosis genes in capsules of failed Ahmed glaucoma valve implants. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5701.
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© ARVO (1962-2015); The Authors (2016-present)
Ahmed glaucoma valve (AGV) implants that are widely used surgical devices in glaucoma have a high risk failure within five years following implantation. An impervious encapsulation of the shunt plate leads to increased hydraulic resistance preventing drainage of aqueous humor and resulting in IOP elevation. We hypothesized that alterations in gene expression in the fibrosis pathway contributes to capsular resistance. We tested this hypothesis by studying fibrosis related gene expression in capsules of failed AGV implants.
Excised capsules obtained during surgical revision of AGV implants for uncontrolled glaucoma were compared with normal control tenon tissues. Total RNA was extracted and purified with RNAqueous-Micro Kit (Ambion). RNA was quantitated and assessed for integrity using NanoDrop 1000 (Thermo Scientific) and Agilent 2100 Bioanalyzer, respectively. Total RNA with RIN of >5.0 was processed for real time PCR quantitation on ViiA7 system (Applied Biosystems) using the RT2 Profiler PCR Array (Qiagen) consisting of a panel of 84 key genes involved in fibrosis. Relative gene expression was calculated using ΔΔCT method.
We examined 5 excised capsules of failed AGV implants and 2 age-matched control tenon specimens. The time to excision ranged from 17 to 48 months after the AGV implant (FP-7 model). We observed differential expression in several genes in the fibrosis pathway. In particular, 33 genes showed altered expression (≥2 fold) in ≥60% of excised capsules. Due to inherent inter-sample biological variability and low statistical power the test of significance was inconclusive. However, notably ≥2 fold upregulation of CTGF, IL13RA2, CCL11, INHBE and THBS1 genes was seen in all 5 excised capsules. Also, ≥ 2 fold upregulation of COL3A1, MMP3, MMP8, SERPINE1 and THBS2 was seen in 4/5 cases. Fifteen other genes were overexpressed in 3/5 cases. IFNG and IL1A showed downregulation in 4/5 excised capsules, while 6 other genes exhibited lower expression in 3/5 cases.
These pathway-focused analyses identified candidate genes that are up and down regulated providing molecular evidence of alterations in the fibrosis pathway in AGV failure. Further validation of identified genes would help to elucidate underlying mechanisms and identify potential therapeutic targets for long term success of AGV implants.
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