Minoxidil inhibits ocular cell proliferation and lysyl hydroxylase activity.
OBJECTIVE
To examine the antiproliferative and lysyl hydroxylase-suppressing effects of minoxidil on cultured proliferating and density-arrested human retinal pigment epithelial cells (hRPE) and Tenon's capsule fibroblasts (hTCF).


METHODS
Proliferating and density-arrested hRPE and hTCF, exposed to minoxidil (0.1-5 mM) for 15 min to 7 days, were examined by proliferation assays, [3H]thymidine incorporation, trypan-blue exclusion, and phase-contrast microscopy. The lysyl hydroxylase-suppressing effects were examined in confluent hRPE exposed to minoxidil (0.01-1 mM) using L-[4,5-3H]-lysine-labeled procollagen substrate and measuring the amount of tritium released as 3H2O after vacuum distillation.


RESULTS
Minoxidil (0.1-5 mM) inhibited the proliferation of subconfluent cultures of hRPE and hTCF in a dose-dependent manner with a half-maximal effect at 1.5 and 2.5 mM, respectively. The antiproliferative effect, detectable within 24 hr, occurred with a limited exposure period and persisted even after removal of minoxidil from the culture medium. In contrast, 1-5 mM minoxidil had minimal effect on density-arrested hRPE and hTCF. However, at doses above 3 mM, although minoxidil had no effect on the number of density-arrested hRPE, morphologic and viability experiments indicated signs of cytotoxicity. Minoxidil (0.1-1 mM) caused a maximum of 71% reduction in the activity of lysyl hydroxylase, an enzyme needed for stable cross-links in collagen.


CONCLUSIONS
Minoxidil may be a useful drug for the treatment of conditions such as proliferative vitreoretinopathy and bleb scarring after trabeculectomy, disorders with unwanted cell proliferation and collagen production.
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
J T
JT
Handa
S
S
Murad
G J
GJ
Jaffe
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004791:Enzyme Inhibitors; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008914:Minoxidil / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000201:enzymology; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000037:antagonists & inhibitors*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D008914:Minoxidil; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase