M. Katsura et al., Growth regulation of bovine retinal pericytes by transforming growth factor-beta 2 and plasmin, CURR EYE R, 20(3), 2000, pp. 166-172
Purpose. Transforming growth factor-beta 2 (TGF-beta 2) is a predominant is
oform of TGF-beta s in the eye and plasmin is a peptidase with many functio
ns. To better understand the pathogenesis of retinal microcirculation disor
ders, the effects of TGF-beta 2 and plasmin on cultured bovine retinal peri
cytes were investigated.
Methods. Exogenous TGF-beta 2 or plasmin was added to some cultures, DNA sy
nthesis during cell cycle progression was investigated using [H-3]thymidine
incorporation. Anti-TGF-beta 2 antibody was added to neutralize the effect
s 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-b
eta 2 and accelerated DNA synthesis, which shows that pericytes regulate th
eir own cell cycle by action of the autocrine and/or paracrine system of TG
F-beta 2. Plasmin (0.2 to 0.5 U/mL) accelerated DNA synthesis in a dose-dep
endent manner, while addition of aprotinin, a protease inhibitor, counterac
ted this effect of plasmin. The concentration of TGF-beta 2 in the culture
medium decreased with the addition of plasmin. Simultaneous addition of bot
h plasmin and anti-TGF-beta 2 antibody accelerated DNA synthesis. High and
low glucose concentrations of the culture medium did not affect DNA synthes
is.
Conclusions. Our results suggest that TGF-beta 2 and plasmin respectively d
ecrease and increase DNA synthesis. In a retinal microcirculation disorder,
they may play competitive roles in the cell cycle of pericytes.