Departments of Surgery, Ophthalmology and Bioengineering, Wake Forest University Health Sciences, Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina.
Graduate School of Pharmaceutical Sciences, School of Pharmacy.
Curr Opin Organ Transplant. 2019 Dec;24(6):726-732. doi: 10.1097/MOT.0000000000000713.
The advent of clinical vascularized composite allotransplantation (VCA), offers hope for whole eye transplantation (WET) in patients with devastating vison loss that fails or defies current treatment options. Optic nerve regeneration and reintegration remain the overarching hurdles to WET. However, the realization of WET may indeed be limited by our lack of understanding of the singular immunological features of the eye as pertinent to graft survival and functional vision restoration in the setting of transplantation.
Like other VCA, such as the hand or face, the eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. The ultimate goal of vision restoration through WET requires optimal immune modulation of the graft for successful optic nerve regeneration. Our team is exploring barriers to our understanding of the immunology of the eye in the context of WET including the role of immune privilege and lymphatic drainage on rejection, as well as the effects ischemia, reperfusion injury and rejection on optic nerve regeneration.
Elucidation of the unique immunological responses in the eye and adnexa after WET will provide foundational clues that will help inform therapies that prevent immune rejection without hindering optic nerve regeneration or reintegration.
临床血管化复合组织同种异体移植(VCA)的出现为治疗那些因目前治疗方法失败或无效而导致严重视力丧失的患者带来了全眼球移植(WET)的希望。视神经再生和再整合仍然是 WET 的主要障碍。然而,WET 的实现可能确实受到我们对眼球作为移植中移植物存活和功能视力恢复相关的独特免疫学特征的理解不足的限制。
像手或脸等其他 VCA 一样,眼睛包括具有不同胚胎谱系和抗原性的多种组织。通过 WET 恢复视力的最终目标需要对移植物进行最佳的免疫调节,以实现成功的视神经再生。我们的团队正在探索在 WET 背景下理解眼睛免疫学的障碍,包括免疫特权和淋巴管引流对排斥的作用,以及缺血、再灌注损伤和排斥对视神经再生的影响。
阐明 WET 后眼睛和附属器的独特免疫反应将提供基础性线索,有助于为预防免疫排斥而不阻碍视神经再生或再整合的治疗方法提供信息。