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.
Handa
J T
JT
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
Murad
S
S
Jaffe
G J
GJ
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