Aqueous Humor TGF-β2 and Its Association With Intraocular Pressure in a Naturally Occurring Large Animal Model of Glaucoma

PURPOSE: Transforming growth factor (TGF)-β2 has been widely implicated in human glaucoma pathology. The purpose of this study was to determine the source of TGF-β2 in aqueous humor (AH) and its relationship with intraocular pressure (IOP) in an inherited large animal model of glaucoma. METHODS: Sixty-six glaucomatous cats homozygous for LTBP2 mutation, and 42 normal cats were studied. IOP was measured weekly by rebound tonometry. AH was collected by anterior chamber paracentesis from each eye under general anesthesia, and serum samples collected from venous blood concurrently. Concentrations of total, active and latent TGF-β2 in AH and serum samples were measured by quantitative sandwich immunoassay. For comparisons between groups, unpaired t-test or Mann Whitney test were used, with P < 0.05 considered significant. The relationships between TGF-β2 concentrations and IOP values were examined by Pearson's correlation coefficient and generalized estimating equation. RESULTS: IOP and AH TGF-β2 concentrations were significantly higher in glaucomatous than in normal cats. AH TGF-β2 showed a significant, robust positive correlation with IOP in glaucomatous cats (r = 0.83, R(2) = 0.70, P < 0.0001). Serum TGF-β2 did not correlate with AH TGF-β2 and was not significantly different between groups. TGF-β2 mRNA and protein expression were significantly increased in local ocular tissues in glaucomatous cats. CONCLUSIONS: Enhanced, local ocular production of TGF-β2 with a robust positive association with IOP was identified in this spontaneous feline glaucoma model, providing a foundation for preclinical testing of novel therapeutics to limit disease-associated AH TGF-β2 elevation and signaling in glaucoma.