Beijing Tongren Eye Centre, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Lab, Beijing, China.
Xenotransplantation. 2011 Jan-Feb;18(1):46-55. doi: 10.1111/j.1399-3089.2011.00626.x.
To compare the immunogenicity of fresh preserved and dehydrated lamellar porcine corneas in porcine-to-mouse heterotopic transplantation and to investigate the survival of preserved porcine corneas as xenografts in porcine-to-rhesus lamellar corneal transplantation.
Dehydrated and fresh preserved, endothelium deprived, porcine corneas were cut into fragments and grafted beneath the kidney capsule of BALB/c mice. Porcine-specific delayed type hypersensitivity (DTH) and antibody (IgM, IgG) immune responses of the recipient mice were assessed. In addition, fresh preserved and dehydrated porcine corneas were used in porcine-to-rhesus lamellar corneal xenotransplantation. The rhesus recipients were divided into three groups. Dehydrated corneas were applied to Group 1 and 3, and fresh preserved corneas were applied to Group 2. Only Group 3 received subconjunctival injections with triamcinolone acetonide for 1 month. All xenografts were evaluated by slit-lamp microscopy for 6 months. Two recipients in each group were examined by in vivo confocal microscopy and then killed for corneal histopathological staining 3 months after surgery.
Neither fresh preserved nor dehydrated corneal fragments evoked any measurable change in mice recipient humoral immune status, but both could induce porcine-specific DTH at 1, 2, and 4 week after being grafted. However, the intensity of the DTH responses evoked by dehydrated corneas was lower than that evoked by fresh preserved corneas. In porcine-to-rhesus lamellar keratoplasty, with the exception one graft in Group 2 that developed characteristics of rejection, all the xenografts remained transparent or translucent up to 6 month after surgery. Histopathological examination of Group 1 showed that the infratemporal xenografts were much thicker and displayed some inflammatory cell infiltration in the peripheral portion of the graft and bed interface. However, in Group 3, which was treated with triamcinolone acetonide, there was an easily identified scar at the lamellar interface with no inflammatory cells present. In the rejected graft in Group 2, infiltrating cells included a few eosinophils and massive lymphocytes. Confocal microscopy examination showed that activated keratocytes localized in the anterior stroma and highly reflective tissue at the interface of the graft and bed.
Porcine corneas might be an ideal source for clinical lamellar corneal xenotransplantation. In cases of tectonic lamellar transplantation, the possibility to use dehydrated pig material may become an option in the future.
比较新鲜保存和脱水猪角膜板层在猪-鼠异位移植中的免疫原性,并研究保存的猪角膜作为异种移植物在猪-恒河猴角膜板层移植中的存活情况。
将去内皮的脱水和新鲜保存的猪角膜切成碎片,移植到 BALB/c 小鼠肾包膜下。评估接受者小鼠的猪特异性迟发型超敏反应(DTH)和抗体(IgM、IgG)免疫反应。此外,新鲜保存和脱水的猪角膜用于猪-恒河猴角膜异种移植。恒河猴受体分为三组。脱水角膜应用于第 1 组和第 3 组,新鲜保存的角膜应用于第 2 组。仅第 3 组接受曲安奈德结膜下注射 1 个月。所有异种移植物在 6 个月内通过裂隙灯显微镜进行评估。每组各有 2 名受体接受体内共聚焦显微镜检查,然后在手术后 3 个月处死进行角膜组织病理学染色。
新鲜保存或脱水的角膜碎片均未引起小鼠受体体液免疫状态的任何可测量变化,但两者均能在移植后 1、2 和 4 周诱导猪特异性 DTH。然而,脱水角膜诱导的 DTH 反应的强度低于新鲜保存角膜诱导的 DTH 反应的强度。在猪-恒河猴板层角膜移植中,除第 2 组中的 1 个移植物出现排斥特征外,所有异种移植物在手术后 6 个月内仍保持透明或半透明。第 1 组的组织病理学检查显示,颞下异种移植物较厚,移植物和床界面的周边部分有一些炎症细胞浸润。然而,在接受曲安奈德治疗的第 3 组中,在板层界面有一个容易识别的疤痕,没有炎症细胞存在。在第 2 组中排斥的移植物中,浸润细胞包括少数嗜酸性粒细胞和大量淋巴细胞。共聚焦显微镜检查显示,活化的角膜细胞定位于前基质和移植物与床界面的高反射组织中。
猪角膜可能是临床板层角膜异种移植的理想来源。在板层移植中,将来可能有使用脱水猪材料的可能性。