Research Group

  • Prof. Reza Dana, Principal Investigator
  • Prof. Andrius Kazlauskas, Co-Investigator
  • Dr. Ying Qian, Research Assistant
  • Mr. Qiang Zhang, Research Technician

Location

  • Schepens Eye Research Institute, Boston, USA

Title

  • Promotion of Corneal Transplant Survival by Anti-Apoptotic Genes

Corneal transplantation is by far the most common form of tissue transplantation. While many grafts have a generally favorable prognosis under topical immune suppression, the medications used to prevent graft failure are toxic to the eye, commonly causing cataracts and glaucoma. In addition, many corneal grafts performed in inflamed host beds are deemed high-risk by virtue of their dismal prognosis due to rejection rates that far exceed 50%.

Corneal clarity is critically dependent upon normal functioning of a monolayer of cells known as the corneal endothelium. These cells are responsible for the pump function that keeps the cornea free from swelling. Almost all forms of corneal transplant failure are due to endothelial cell dysfunction or death. Moreover, many endothelial cells are lost in the process of eye banking prior to transplantation, so that the grafted donor tissue becomes particularly vulnerable to failure if its endothelium comes under immune attack.

Corneal endothelial cell death is mediated by a process known as apoptosis. Many of the genes responsible for apoptosis have been defined, as have genes that downregulate this process – known as anti-apoptotic genes. Gene therapy is the strategy by which selective genes are either activated or downregulated. Our preliminary work shows great promise in using a viral vector to selectively infect corneal endothelial cells with the desired genes after organ procurement but before transplantation. We propose to use this strategy to overexpress anti-apoptotic genes in the endothelium so as to render grafted corneas resistant to a variety of stresses, including those that lead to cell death during storage or immune-mediated cell death after transplantation.

We hope that successful completion of our proposal will lead to significant enhancement of graft survival, even in the adverse setting of high-risk transplantation, as well as better organ preservation over longer periods.