Article
Anti-angiogenic effect of Mycophenolate mofetil in inhibition of neovascularization in cornea
Search Medline for
Authors
Published: | September 22, 2004 |
---|
Outline
Text
Objective
Clinical observations reveald that the immunosuppressive drug mycophenolate mofetil (MMF) has a potential to inhibit neovascularization of corneal transplants in patients. This study focussed on the influence of MMF on cellular outgrowth and tube formation in corneal tissues in a three dimensional Matrigel™ invasion assay and tube formation assay.
Methods
10 vascularized corneas from patients undergoing keratoplasty were considered as case group and 5 non-vascularized donor corneas unsuitable for keratoplasty served as control. Each cornea was divided into three parts for immunohistochemistry, western blot analysis and three dimensional tissue culture.
Results
Case group: Histological analysis showed a high number of blood vessels in the case group with positive staining for CD31, CD34 and vWF. Western blot analysis of isolated corneal cells demonstrated expression of carcinoembryogenic antigen cell adhesion molecule 1 (CEACAM1) and integrin β3. In three dimensional culture of cornea, many fibroblastoid cells migrated into the collagen matrix after 2 d. Vascular-like sprouting and tube formation was visible in collagen gel after 7 d, these structures were observable by phase contrast microscopy for up to 15 d. A 2 d treatment with 0,5-1 μM MMF solution inhibited tube formation. Control group: Outgrowth of fibroblastoid cells, but no tube formation, could be observed.
Conclusions
The assay proves to be useful for further investigation of the possible antiangiogenetic effect of other drugs. The data show that MMF can inhibit tube formation in vitro and by this way may inhibit neovascularization of corneal grafts, as seen in patients treated with MMF after keratoplasty. This effect might be due to an antiproliferative action on endothelial cells. Besides, the presence of CEACAM 1 and integrin β3 in vascularized corneas suggests they play a role in angiogenic processes in the human cornea.