Barcia R N, Dana M R, Kazlauskas A
Schepens Eye Research Institute, Harvaard Medical School, 20 Staniford St, Boston, MA, USA.
Am J Transplant. 2007 Sep;7(9):2082-9. doi: 10.1111/j.1600-6143.2007.01897.x. Epub 2007 Jul 5.
Corneal transplants normally enjoy a high percentage of survival, mainly because the eye is an immune-privileged site. When allograft failure occurs, it is most commonly due to rejection, an immune-mediated reaction that targets the corneal endothelium. While the exact mechanism by which the endothelium is targeted is still unknown, we postulate that corneal endothelial cell loss during allograft failure is mediated by apoptosis. Furthermore, because corneal endothelial cells do not normally regenerate, we hypothesize that suppressing apoptosis in the graft endothelium will promote transplant survival. In a murine model of transplantation, TUNEL staining and confocal microscopy showed apoptosis of the graft endothelium occurring in rejecting corneas as early as 2 weeks posttransplantation. We found that bcl-xL protected cultured corneal endothelial cells from apoptosis and that lentiviral delivery of bcl-xL to the corneal endothelium of donor corneas significantly improved the survival of allografts. These studies suggest a novel approach to improve corneal allograft survival by preventing apoptosis of the endothelium.
角膜移植通常具有很高的存活率，主要是因为眼睛是一个免疫赦免部位。当同种异体移植失败时，最常见的原因是排斥反应，这是一种针对角膜内皮的免疫介导反应。虽然内皮细胞被靶向的确切机制仍不清楚，但我们推测同种异体移植失败期间角膜内皮细胞的损失是由凋亡介导的。此外，由于角膜内皮细胞通常不会再生，我们假设抑制移植内皮细胞中的凋亡将促进移植存活。在一个小鼠移植模型中，TUNEL染色和共聚焦显微镜显示，早在移植后2周，排斥的角膜中就出现了移植内皮细胞的凋亡。我们发现bcl-xL可保护培养的角膜内皮细胞免于凋亡，并且将bcl-xL通过慢病毒递送至供体角膜的内皮细胞可显著提高同种异体移植的存活率。这些研究提示了一种通过防止内皮细胞凋亡来提高角膜同种异体移植存活率的新方法。
