Professor Buckley has been awarded a 2017 University Research Award to pursue a promising project that has the potential to eventually leverage external funding. He will evaluate two approaches to minimizing the loss of corneal endothelial cells during cornea transplants. The project is titled, "Protection of corneal endothelial cells from surgical trauma."
More than 65,000 vision-restoring corneal transplantations take place every year for individuals with corneal disease, corneal injury (e.g., from cataract surgery) and corneal scarring. Unfortunately, 30% of corneal grafts fail within 20 years. The most common reason for transplanted corneal grafts to fail is loss of corneal endothelial cells (CECs), the cells that line the inside of the cornea and pump fluid from it to maintain its transparency. Many of these cells are killed due to contact with tools and other materials during transplantation surgery. Thus, there is a need for new approaches that prevent CEC death during corneal grafting.
Using a custom testing platform developed in our laboratory, our preliminary experiments suggest that changes in the cytoskeleton (the network of structures within a cell that give it its shape) of CECs greatly protect these cells from injury due to mechanical contact. That is, when cells contain fewer stress fibers -- thick cytoskeletal filaments that, like muscle, exert a contractile force -- mechanical vulnerability is reduced. Based on these findings, we hypothesize treatments known to reduce the presence of stress fibers in cells will protect CECs from mechanical injury during corneal transplantation. In Aim 1, we will test whether chemical treatment with three agents that interfere with stress fibers -- BAPTA, blebbistatin and the anti-metabolite 5-fluorouracil -- reduces CEC death when the endothelium is contacted with a controlled force (simulating surgical manipulation). In Aim 2, motivated by the previous finding that fewer CEC stress fibers are observed in corneas preserved at low temperatures, we will test whether CECs are less vulnerable to mechanical trauma when the cornea is colder. This study is a key first step towards establishing chemical treatments (Aim 1) and maintenance of the cornea at cold temperatures during surgery (Aim 2) as promising methods to limit surgical trauma-associated CEC loss during corneal transplantation and reduce risk of graft failure. These approaches may also be applicable to other eye surgeries that can damage the corneal endothelium, including cataract surgery.