February 1994
Volume 35, Issue 2
Free
Articles  |   February 1994
Inhibition of cultured human RPE cell proliferation and lysyl hydroxylase activity by hydroxy derivatives of minoxidil.
Author Affiliations
  • J T Handa
    Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
  • S Murad
    Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
  • G J Jaffe
    Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
Investigative Ophthalmology & Visual Science February 1994, Vol.35, 463-469. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J T Handa, S Murad, G J Jaffe; Inhibition of cultured human RPE cell proliferation and lysyl hydroxylase activity by hydroxy derivatives of minoxidil.. Invest. Ophthalmol. Vis. Sci. 1994;35(2):463-469.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

PURPOSE: To examine the antiproliferative and lysyl hydroxylase suppressing effects of 3'-hydroxyminoxidil and 4'-hydroxyminoxidil, derivatives of minoxidil devoid of the antihypertensive effect, on human retinal pigment epithelial (RPE) cells in culture. METHODS: Subconfluent and confluent cultures of RPE cells, exposed to 0.01 to 5 mM 3' or 4'-hydroxyminoxidil for 15 minutes to 7 days, were examined for proliferation, viability, and morphologic changes. Lysyl hydroxylase activity in confluent cultures exposed to 1 mM 3'- or 4'-hydroxyminoxidil was determined by measuring the amount of 3H2O released from L-(4,5-3H)lysine-labeled unhydroxylated procollagen substrate after vacuum distillation. RESULTS: Both compounds inhibited the proliferation of subconfluent cultures of RPE cells in a dose-dependent fashion. The 50% effect occurred at 0.25 mM for 3'-hydroxyminoxidil and 0.5 mM for 4'-hydroxyminoxidil. The antiproliferative effect was detectable within 24 hours, required a minimum 1-hour exposure, and persisted even after the drug was removed from the culture medium. Cell viability experiments provided no evidence for toxicity. In contrast, the number of cells at confluent density was not affected. Both 3'-hydroxyminoxidil and 4'-hydroxyminoxidil suppressed lysyl hydroxylase activity by 72%. CONCLUSIONS: The structure of minoxidil can be altered to reduce the antihypertensive activity while preserving the antiproliferative and lysyl hydroxylase suppressing effects. The hydroxy derivatives of minoxidil may be useful in the treatment of proliferative vitreoretinopathy, a disease with unwanted proliferation of RPE cells.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×