Departments of Surgery, Ophthalmology and Bioengineering, Wake Forest University Health Sciences, Wake Forest Institute for Regenerative Medicine, Winston Salem, NC, USA; Department of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Ankara, Turkey.
Department of Plastic and Reconstructive Surgery, Gulhane Military Medical Academy, Ankara, Turkey.
J Plast Reconstr Aesthet Surg. 2019 Oct;72(10):1640-1650. doi: 10.1016/j.bjps.2019.05.042. Epub 2019 Jun 18.
Whole eye transplantation (WET) holds promise for vision restoration in devastating/disabling visual loss (congenital or traumatic) not amenable to surgical or neuroprosthetic treatment options. The eye includes multiple tissues with distinct embryonic lineage and differential antigenicity. Anatomically and immunologically, the eye is unique due to its avascular (cornea) and highly vascular (retina) components. Our goal was to establish technical feasibility, demonstrate graft viability, and evaluate histologic changes in ocular tissues/adnexae in a novel experimental model of WET that included globe, adnexal, optic nerve (ON), and periorbital soft tissues.
Outbred Sprague-Dawley rats (n = 5) received heterotopic vascularized WET from donors. Each WET included the entire globe, adnexa, ON, and periorbital soft tissues supplied by the common carotid artery and external jugular vein. Viability and perfusion were confirmed by clinical examination, angiography and magnetic resonance imaging (MRI). Globe, adnexal, and periorbital tissues were analyzed for histopathologic changes, and the ON was examined for neuro-regeneration at study endpoint (30 days) or Banff Grade 3 rejection in the periorbital skin (whichever was earlier).
Gross examination confirmed transplant viability and corneal transparency. Average operative duration was 64.0 ± 5.8 min. Average ischemia time was 26.0 ± 4.2 min. MRI revealed loss of globe volume by 36.0 ± 2.8% after transplantation. Histopathology of globe and adnexal tissues showed unique and differential patterns of inflammatory cell infiltration. The ON revealed a neurodegeneration pattern.
The present study is the first in the literature to establish an experimental model of WET. This model holds significant potential in investigating mechanistic pathways, monitoring strategies or developing management approaches involving ocular viability, immune rejection, and ON regeneration after WET.
全眼球移植(WET)有望为无法通过手术或神经假体治疗的严重/致盲性视力丧失(先天性或外伤性)恢复视力。眼睛包含具有不同胚胎谱系和不同抗原性的多种组织。从解剖学和免疫学角度来看,由于眼睛具有无血管(角膜)和高度血管(视网膜)成分,因此它是独特的。我们的目标是在包括眼球、附属物、视神经(ON)和眼眶软组织的新型 WET 实验模型中建立技术可行性,证明移植物的活力,并评估眼部组织/附属物的组织学变化。
杂种 Sprague-Dawley 大鼠(n=5)接受了供体的异位血管化 WET。每个 WET 包括整个眼球、附属物、ON 和由颈总动脉和颈外静脉供应的眼眶软组织。通过临床检查、血管造影和磁共振成像(MRI)确认活力和灌注。在研究终点(30 天)或眼眶皮肤发生 3 级排斥反应(以先发生者为准)时,分析眼球、附属物和眼眶组织的组织病理学变化,并检查 ON 的神经再生情况。
大体检查证实了移植物的活力和角膜的透明度。平均手术时间为 64.0±5.8 分钟。平均缺血时间为 26.0±4.2 分钟。MRI 显示移植后眼球体积减少 36.0±2.8%。眼球和附属物组织的组织病理学显示出独特和不同的炎症细胞浸润模式。ON 显示出神经退行性变模式。
本研究首次在文献中建立了 WET 的实验模型。该模型在研究涉及 WET 后眼部活力、免疫排斥和 ON 再生的机制途径、监测策略或开发管理方法方面具有重要潜力。