The effect of minoxidil on keratocyte proliferation in cell culture

Document Type

Article

Publication Date

7-1-1998

Abstract

Purpose: To determine if minoxidil inhibits keratocyte proliferation in a nontoxic manner. Methods: Rabbit keratocytes were cultured in Eagle's minimum essential medium supplemented with fetal bovine serum. Minoxidil varying in concentration from 100 to 103 μg/ml was added to the culture medium and incubated for 7 days. The cultures were inspected for morphologic appearance and the cell number was determined at 1, 3 and 7 days after the addition of minoxidil. After 7 days of incubation, minoxidil was withdrawn from the cell culture medium and the cells were examined 3 and 7 days thereafter. In addition, a nonradioactive cytotoxic assay was performed to determine if toxicity is associated with the presence of minoxidil. Results: Minoxidil inhibited keratocyte proliferation in a dose-dependent fashion. 29% of control growth was achieved when keratocytes were cultured for 7 days in 103 μg/ml, whereas 82% control growth was achieved when keratocytes were cultured in 102 μg/ml of minoxidil. Intermediate concentrations between 102 and 103 μg/ml produced a linear decline in cell counts in a dose-dependent fashion. The concentration of minoxidil required for 50% control growth at 7 days extrapolated from the dose-response curve was 600 μg/ml. Upon withdrawal of minoxidil, cell counts returned to baseline for concentrations of 102 μg/ml or less. Phase contrast microscopy revealed that the presence of minoxidil was associated with intercellular separation, enlargement of cell bodies and elongated processes. After the withdrawal of minoxidil, the cells in all media reassumed the morphological features of normal keratocytes which included a regular fusiform shape and extensive intercellular contact. The nonradioactive cytotoxic assay revealed the lack of cytotoxicity at all concentrations of minoxidil based on a lack of lactate dehydrogenase release. Conclusions: Minoxidil inhibits keratocyte proliferation by a nontoxic mechanism. It might be particularly useful for modulating corneal wound healing following excimer laser photorefractive keratectomy.

Publication Source (Journal or Book title)

Ophthalmic Research

First Page

263

Last Page

270

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