RESUMO
AIM: To determine the involvement of the transforming growth factor (TGF)-ß with the development of experimental subretinal fibrosis in a mouse model. METHODS: Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells (PECs) and the local expression of TGF-ß isoforms was assessed by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) at various time points. In addition, we investigated the effect of TFG-ß-neutralizing antibodies (TGF-ß NAb) on subretinal fibrosis development. RESULTS: TGF-ß1 and TGF-ß2 mRNA level was significantly elevated at day 2 after subretinal fibrosis induction and increased further to 5 and 6.5-fold respectively at day 5, reaching the peak. TGF-ß3 mRNA was not detected in the present study. The result of ELSIA showed that active TGF-ß1 and TGF-ß2 levels were upregulated to 10-fold approximately, while total TGF-ß1 and TGF-ß2 levels were even upregulated more than 10-fold and more than 20-fold respectively in subretinal fibrosis mice in comparison with naïve mice at day 5. TGF-ß NAb resulted in a reduced subretinal fibrosis areas by 65% compared to animals from control group at day 7. CONCLUSION: Our results indicate that TGF-ß signaling may contribute to the pathogenesis of subretinal fibrogenesis and TGF-ß inhibition may provide an effective, novel treatment of advanced and late-stage neovascular age-related macular degeneration.