OPC-15161 suppresses the proliferation of Tenon's capsule fibroblasts and the production of type I collagen and fibronectin stimulated by TGF-beta1 in vitro.
OBJECTIVE
We investigated the effects of OPC-15161 on the growth of cultured human Tenon's capsule fibroblasts (TCFs), as well as on the production of type I procollagen, fibronectin, and laminin. These effects were examined in the presence or absence of TGF-beta1.


METHODS
Cell proliferation was assayed by counting cell number and assay of DNA synthesis. Cytotoxicity was determined by the MTT method. Matrix components were assayed by enzyme immunoassay of material in the medium and in the cell lysate with or without OPC-15161. Total protein content was determined. Cellular ultrastructure was also evaluated.


RESULTS
Treatment with OPC-15161 (up to 100.0 microg ml(-1)) significantly reduced the proliferation and DNA synthesis of TCFs. No significant decrease in MTT values was observed in confluent TCF cultures with OPC-15161 (up to 100.0 microg ml(-1)). TGF-beta1 enhanced the TCF production of procollagen I and fibronectin. OPC-15161 significantly decreased the procollagen I content in both the medium, in the cell lysate of TGF-beta1-stimulated cells, and fibronectin content in the lysate. OPC-15161 did not affect the laminin or total protein content, either with or without TGF-beta1. No ultrastructural evidence of cytotoxicity was observed.


CONCLUSIONS
OPC-15161 inhibited the proliferation of TCFs, and reduced their production of procollagen I and fibronectin in the presence of TGF-beta1 without evidence of cytotoxicity. OPC-15161 may be useful in inhibiting the excessive fibrosis produced in the wound in response to filtering surgery.
Saika
S
S
Department of Ophthalmology, Wakayama Medical College, Japan.
Yamanaka
O
O
Kawashima
Y
Y
Ohkawa
K
K
Ohnishi
Y
Y
Ooshima
A
A
Kimura
M
M
Nakano
Y
Y
Kao
W W
WW
D000328:Adult; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004261:DNA Replication / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005353:Fibronectins / Q000096:biosynthesis*; D006801:Humans; D007797:Laminin / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000096:biosynthesis*; D011719:Pyrazines / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D005353:Fibronectins; D007797:Laminin; D011347:Procollagen; D011719:Pyrazines; D013778:Tetrazolium Salts; D013844:Thiazoles; D016212:Transforming Growth Factor beta; C067708:OPC 15161; C022616:thiazolyl blue