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Kazuya Oikawa, David Sun, Julie A Kiland, Elizabeth Hennes-Beean, Ralph Trane, Gillian J McLellan; Association between aqueous humor (AH) Transforming Growth Factor (TGF)-β and intraocular pressure (IOP) in a spontaneous glaucoma model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3525.
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© ARVO (1962-2015); The Authors (2016-present)
TGF-β has been widely implicated in glaucoma pathobiology. Studies report higher TGF-β in AH of glaucoma patients, but its association with IOP has not been established. We sought to determine the relationship between AH TGF-β concentration and IOP in spontaneous feline congenital glaucoma (FCG), and if serum TGF-β is predictive of AH TGF-β in cats.
Twenty-five LTBP2-/- feline congenital glaucoma (FCG; 11 male,14 female) and 19 wild type cats (13 male, 6 female) were studied. IOP was measured (TonoVet, ICare Oy) 3x/week from 10 weeks - 6 months of age and weekly thereafter. AH was collected by anterior chamber paracentesis from each eye under general anesthesia, and serum samples collected from venous blood concurrently, and both were stored at -80°C until analysis. Concentrations of total TGF-β2 in AH and serum samples were measured by quantitative sandwich immunoassay (TGF-β2 Quantikine® ELISA, R&D Systems). For the purposes of statistical analyses, mean IOP over 4 weeks prior to AH tap, and average of duplicate values of TGF-β were calculated. For comparisons between groups, student t-test or Mann Whitney test were used, with p < 0.05 considered significant. The relationship between serum and AH TGF-β was examined by linear regression. IOP was modeled as a function of sex, genotype, age, and rescaled AH TGF-β2 concentrations, including an interaction effect between glaucoma and AH TGF-β2 concentration. The model was fitted using generalized estimating equations with cat identifier as ID variable, and an exchangeable correlation structure.
In total, 136 AH and 58 serum samples were analyzed. In FCG, IOP was significantly higher than controls from 2 months of age (Mann-Whitney test; p < 0.0001), and rescaled AH TGF-β2 showed significant positive correlation with IOP (estimate slope = 1.8989; p < 0.0001), while in normal cats AH TGF-β2 was negatively correlated with IOP (slope = -1.1688; p < 0.0293). Serum TGF-β2 was not significantly different between FCG and controls and weakly correlated with AH TGF-β2 (r2 = 0.14, p = 0.02).
Our results confirm local ocular production of TGF-β2 in FCG, and strong association between AH TGF-β and IOP in glaucoma, though whether this represents cause or effect remains to be determined. Initial findings do not support measurement of serum TGF-β2 as a biomarker in glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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