Antiproliferative effect of mycophenolate mofetil on cultured human Tenon fibroblasts

Graefes Arch Clin Exp Ophthalmol. 2002 May;240(5):408-14. doi: 10.1007/s00417-002-0452-4. Epub 2002 Mar 12.

Abstract

Background: Wound healing after glaucoma filtering surgery is often complicated by exaggerated scarring of the subconjunctival Tenon's layer. Therefore, antiproliferatives are commonly employed. The immunosuppressive drug mycophenolate mofetil (MMF) is used to prevent graft rejection after kidney or liver transplantation. The effect is mediated by inhibition of lymphocyte proliferation. In this study we investigated the effect of MMF on human Tenon fibroblast proliferation in cell culture.

Methods: Human Tenon fibroblasts (HTF) were cultivated with 10% fetal calf serum. Cells were incubated with MMF concentrations of 0.1 microM to 3000 microM for up to 20 days. In a second set of experiments HTF were incubated for 10 min only in MMF solutions. Cell counts were performed to evaluate the proliferation rate. The proliferation was also assessed by Ki67 staining. Morphological changes were documented by vimentin staining.

Results: Growth inhibition of HTF by MMF was concentration dependent. IC(50) was 0.85+/-0.05 microM for 6 days of incubation. Brief exposure to MMF leads to a reversible growth arrest for up to 14 days with concentrations of 1000 microM or higher. Ki67 staining confirmed the concentration dependent proliferation rate.

Conclusion: MMF has a concentration-dependent antiproliferative effect on HTF without any detected cytotoxicity in the applied concentration range. Brief incubation also leads to a growth arrest; therefore, intraoperative MMF application might prevent exaggerated scarring after glaucoma filtering surgery.

MeSH terms

  • Aged
  • Cell Count
  • Cell Division / drug effects
  • Cells, Cultured
  • Connective Tissue
  • Dose-Response Relationship, Drug
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Ki-67 Antigen / metabolism
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology*

Substances

  • Immunosuppressive Agents
  • Ki-67 Antigen
  • Mycophenolic Acid