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Updated: Aug 25, 2026
Murine Corneal Transplantation: A Model to Study the Most Common Form of Solid Organ Transplantation
Published on: November 17, 2014
Effect of metalloprotease inhibitors on corneal allograft survival
Patrick M Stuart1, Fan Pan, Xiaotang Yin
1Department of Ophthalmology, Washington University Medical School, St Louis, Missouri 63110, USA. stuart@vision.wustl.edu
Purpose:
The expression of Fas ligand (FasL) in the cornea is essential for corneal allograft acceptance in mice. Because the expression of FasL on the surface of cells is sensitive to cleavage with matrix metalloproteases (MMPs), this study examined whether inhibitors of MMPs would lead to increased FasL expression and improved corneal allograft survival.
Methods:
Corneal endothelia derived from mice and humans were treated with MMP inhibitors, and FasL expression was examined. BALB/c mice were engrafted with C57BL/6 or C57BL/6-gld corneas and treated with an ointment containing the MMP inhibitor, doxycycline. Corneal allograft survival was monitored for 50 days.
Results:
Corneal endothelial cells from both mice and humans displayed increased surface expression of FasL after treatment with MMP inhibitors. The increase in surface expression was further evidenced by the ability of these cells to kill Fas-expressing target cells. Mice treated with doxycycline after corneal allograft transplantation showed significantly prolonged allograft survival and an increase in the overall acceptance rate.
Conclusions:
MMP inhibitor treatment of cornea-derived endothelial cells results in increased FasL expression and function. MMP inhibitor treatment prolongs corneal allograft survival and results in a modest increase in corneal allograft acceptance.
Insights
Matrix metalloprotease (MMP) inhibitors increase Fas ligand (FasL) expression on corneal endothelial cells. This leads to improved corneal allograft survival and acceptance in mice, offering a potential therapeutic strategy.
Area of Science:
- Immunology
- Ophthalmology
- Transplantation immunology
Background:
- Fas ligand (FasL) expression in the cornea is crucial for successful corneal allograft acceptance.
- FasL surface expression is vulnerable to cleavage by matrix metalloproteases (MMPs).
Purpose of the Study:
- To investigate if MMP inhibitors can enhance FasL expression.
- To determine if enhanced FasL expression improves corneal allograft survival.
Main Methods:
- Corneal endothelial cells from mice and humans were treated with MMP inhibitors to assess FasL expression.
- Mice received corneal allografts and were treated with doxycycline, an MMP inhibitor, with survival monitored for 50 days.
Main Results:
- MMP inhibitor treatment significantly increased surface FasL expression on corneal endothelial cells from both species.
- Treated cells demonstrated enhanced killing of Fas-expressing target cells.
- Doxycycline treatment prolonged corneal allograft survival and increased acceptance rates in mice.
Conclusions:
- MMP inhibitors enhance FasL expression and function in corneal endothelial cells.
- MMP inhibitor therapy offers a promising approach to improve corneal allograft survival and acceptance.
