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Investigative Ophthalmology & Visual Science, Vol 34, 567-575, Copyright © 1993 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Minoxidil inhibits ocular cell proliferation and lysyl hydroxylase activity

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

PURPOSE. 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.




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Copyright © 1993 by the Association for Research in Vision and Ophthalmology