HTRA1 and TGF-β1 concentrations in the aqueous humor of patients with neovascular age-related macular degeneration

PURPOSE: To evaluate the expression of high-temperature requirement A serine peptidase 1 (HTRA1), transforming growth factor beta 1 (TGF-β1), bone morphogenetic protein 4 (BMP4), growth differentiation factor 6 (GDF6), and vascular endothelial growth factor A (VEGFA) proteins in the aqueous humor of patients with naïve choroidal neovascularization (nCNV) secondary to age-related macular degeneration. METHODS: We measured by ELISA the concentrations of HTRA1, TGF-β1, BMP4, GDF6 and VEGFA in the aqueous humor of 23 patients affected by nCNV who received 3 consecutive monthly intravitreal injections of 0.5 mg ranibizumab. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). 23 age-matched cataract patients served as controls. RESULTS: BMP4 and GDF6 were not detectable in any samples. Baseline HTRA1 was higher than controls (P<0.0001), and higher than both the month 1 (P<0.0001) and the month 2 (P<0.0001) values. Baseline VEGFA was higher than controls (P<0.0001), not different from month 1 value (P=0.0821), but higher than month 2 value (P<0.0001). Baseline TGF-β1 was higher than controls (P=0.0015) and not different from month 1 (P=0.129) and month 2 values (P=0.5529). No correlation was found in naïve patients between concentrations of HTRA1 and TGF-β1, HTRA 1 and VEGFA, or TGF-β1 and VEGFA. CONCLUSIONS: In nCNV patients, HTRA1 and TGF-β1 were significantly higher compared to controls. After treatment, TGF-β1 was persistently elevated, while HTRA1 returned to control levels, suggesting the involvement of TGF-β1 and HTRA1 in nAMD and a VEGFA-independent role for TGF-β1.