Transforming and insulin-like growth factors in the aqueous humour of patients with exfoliation syndrome

Background: Growth factors circulating with the aqueous may play an important role in the pathogenesis of exfoliation syndrome (XFS), which is characterized by excessive synthesis and accumulation of abnormal extracellular material. Methods: We investigated the concentration of three ubiquitous growth factors (TGF-beta1, TGF-beta2 and IGF-1) in the aqueous humour of 50 patients with XFS (27 from Erlangen, 23 from Thessaloniki) and 54 age-matched controls (27 from Erlangen, 27 from Thessaloniki). This study was performed in two centres, independently of each other, using different assay systems. Results: In the aqueous humour samples collected in Erlangen, both the levels of total TGF-beta1 (P<0.001) and mature TGF-<beta>1 (P<0.05) were significantly increased in XFS patients compared with controls. Specifically, for total TGF-<beta>1 patients with XFS exhibited higher a mean value (90.5 +/- 37.4 pg/ml) than controls (30.2 +/-8.3 pg/ml). The mean level of mature TGF-beta1 was also higher in XFS (14.2 +/-2.8 pg/ml) than in controls (4.9 +/-5.5 pg/ml). No difference was found between XFS and controls in the levels of total or mature TGF beta2 in the aqueous or in the level of these two growth factors in the serum. In aqueous humour samples collected in Thessaloniki a significant difference between XFS and controls was also observed for mature TGF-P I (XFS 17.06 +/- 11.02 pg/ml vs controls 9.01 +/-5.69 pg/ml; P=0.006). No difference was observed in TGF-beta2 concentration or IGF-1 concentration in the aqueous. No correlation could be established between protein concentration and the levels of the three growth factors measured. A significant correlation was found between age and protein concentration in XFS, but not in the controls. Conclusion: Since TGF-beta1 induces the synthesis and accumulation of extracellular matrix, it is hypothesized that TGF-beta1 plays an important role in the pathogenesis of XFS. Our data suggest that the increased levels of TGF-beta1 are most likely due to enhanced local synthesis.