TGF-ß concentrations and activity are down-regulated in the aqueous humor of patients with neovascular age-related macular degeneration.

Controversy still exists regarding the role of the TGF-ß in neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Here, we measured the concentrations of active TGF-ß1, TGF-ß2, and TGF-ß3 by ELISA in the aqueous humor of 20 patients affected by nAMD, who received 3 consecutive monthly intravitreal injections of anti-VEGF-A antibody. Samples were collected at baseline (before the first injection), month 1 (before the second injection), and month 2 (before the third injection). The same samples were used in a luciferase-based reporter assay to test the TGF-ß pathway activation. Active TGF-ß1 concentrations in the aqueous humor were below the minimum detectable dose. Active TGF-ß2 concentrations were significantly lower at baseline and at month 1, compared to controls. No significant differences in active TGF-ß3 concentration were found among the sample groups. Moreover, TGF-ß pathway activation was significantly lower at baseline compared to controls. Our data corroborate an anti-angiogenic role for TGF-ß2 in nAMD. This should be considered from the perspective of a therapy using TGF-ß inhibitors.