Growth regulation of bovine retinal pericytes by transforming growth factor-beta2 and plasmin.

Purpose. Transforming growth factor-beta 2 (TGF-beta 2) is a predominant isoform of TGF-beta s in the eye and plasmin is a peptidase with many functions. To better understand the pathogenesis of retinal microcirculation disorders, the effects of TGF-beta 2 and plasmin on cultured bovine retinal pericytes were investigated. Methods. Exogenous TGF-beta 2 or plasmin was added to some cultures, DNA synthesis during cell cycle progression was investigated using [H-3]thymidine incorporation. Anti-TGF-beta 2 antibody was added to neutralize the effects of TGF-beta 2. TGF-beta 2 in the culture medium was measured using enzyme-linked immunosorbent assay (ELISA). Results. Exogenous TGF-beta 2 (10 pg to 100 ng/mL) suppressed DNA synthesis. Pericytes produced TGF-beta 2. Anti-TGF-beta 2 antibody neutralized TGF-beta 2 and accelerated DNA synthesis, which shows that pericytes regulate their own cell cycle by action of the autocrine and/or paracrine system of TGF-beta 2. Plasmin (0.2 to 0.5 U/mL) accelerated DNA synthesis in a dose-dependent manner, while addition of aprotinin, a protease inhibitor, counteracted this effect of plasmin. The concentration of TGF-beta 2 in the culture medium decreased with the addition of plasmin. Simultaneous addition of both plasmin and anti-TGF-beta 2 antibody accelerated DNA synthesis. High and low glucose concentrations of the culture medium did not affect DNA synthesis. Conclusions. Our results suggest that TGF-beta 2 and plasmin respectively decrease and increase DNA synthesis. In a retinal microcirculation disorder, they may play competitive roles in the cell cycle of pericytes.