Abstract：
OBJECTIVE: This study aims to reveal the immunopathogenesis of the high-risk corneal transplantation using a comparative proteomic approach.
METHODS: The immunological properties of ocular tissues (including corneal grafts, aqueous humour, and iris-ciliary body) were analysed using a high-risk rabbit corneal transplantation model employing a comparative proteomic approach.
RESULTS: The corneal grafts revealed a dramatic increase in the immune response both at the early (postoperative day 7) and rejection stages, along with the appearance of transplantation stress-induced cellular senescence in the early stage. The aqueous humour (AH) displayed persistent pathological alterations, indicated by the significant enrichment of complement and coagulation cascades pathway in the early stage and interleukin (IL)-17 signalling pathway in the rejection stage. More surprisingly, the pronounced elevation of immune response was also observed in the iris-ciliary body (I-CB) tissues at the early and rejection stages. The enriched immune-related pathways were associated with antigen processing and presentation, complement and coagulation cascades, and IL-17 signalling pathway. Furthermore, proteomic analysis revealed that the implantation of Cyclosporine A drug delivery system (CsA-DDS) into the anterior chamber obviously mitigated corneal transplantation rejection by inhibiting immunoreaction both in the corneal grafts and I-CB tissues.
CONCLUSIONS: The results highlighted the involvement of intraocular immunity both in the grafts and I-CB tissues during corneal transplantation rejection, further suggesting the anterior chamber as an optimal drug-delivery site for its treatment.
METHODS: The immunological properties of ocular tissues (including corneal grafts, aqueous humour, and iris-ciliary body) were analysed using a high-risk rabbit corneal transplantation model employing a comparative proteomic approach.
RESULTS: The corneal grafts revealed a dramatic increase in the immune response both at the early (postoperative day 7) and rejection stages, along with the appearance of transplantation stress-induced cellular senescence in the early stage. The aqueous humour (AH) displayed persistent pathological alterations, indicated by the significant enrichment of complement and coagulation cascades pathway in the early stage and interleukin (IL)-17 signalling pathway in the rejection stage. More surprisingly, the pronounced elevation of immune response was also observed in the iris-ciliary body (I-CB) tissues at the early and rejection stages. The enriched immune-related pathways were associated with antigen processing and presentation, complement and coagulation cascades, and IL-17 signalling pathway. Furthermore, proteomic analysis revealed that the implantation of Cyclosporine A drug delivery system (CsA-DDS) into the anterior chamber obviously mitigated corneal transplantation rejection by inhibiting immunoreaction both in the corneal grafts and I-CB tissues.
CONCLUSIONS: The results highlighted the involvement of intraocular immunity both in the grafts and I-CB tissues during corneal transplantation rejection, further suggesting the anterior chamber as an optimal drug-delivery site for its treatment.
摘要：
目的：本研究旨在通过比较蛋白质组学方法揭示高危角膜移植的免疫发病机制。
方法：眼组织（包括角膜移植物，房水幽默，和虹膜睫状体）使用比较蛋白质组学方法使用高风险的兔角膜移植模型进行分析。
结果：角膜移植物显示，在早期（术后第7天）和排斥阶段，免疫反应都急剧增加，随着早期移植应激诱导的细胞衰老的出现。房水（AH）表现出持续的病理改变，补体和凝血级联通路在早期阶段的显著富集和白细胞介素（IL）-17信号通路在排斥阶段的显著富集。更令人惊讶的是,在早期和排斥阶段，在虹膜睫状体（I-CB）组织中也观察到免疫反应的显着升高。丰富的免疫相关途径，包括抗原加工和呈递，补体和凝血级联，和IL-17信号通路。此外，蛋白质组学分析表明，将环孢素A药物递送系统（CsA-DDS）植入前房通过抑制角膜移植物和I-CB组织中的免疫反应，明显减轻了角膜移植排斥反应。
结论：结果强调了角膜移植排斥过程中移植物和I-CB组织的眼内免疫受累，进一步表明前房作为其治疗的最佳药物递送部位。
方法：眼组织（包括角膜移植物，房水幽默，和虹膜睫状体）使用比较蛋白质组学方法使用高风险的兔角膜移植模型进行分析。
结果：角膜移植物显示，在早期（术后第7天）和排斥阶段，免疫反应都急剧增加，随着早期移植应激诱导的细胞衰老的出现。房水（AH）表现出持续的病理改变，补体和凝血级联通路在早期阶段的显著富集和白细胞介素（IL）-17信号通路在排斥阶段的显著富集。更令人惊讶的是,在早期和排斥阶段，在虹膜睫状体（I-CB）组织中也观察到免疫反应的显着升高。丰富的免疫相关途径，包括抗原加工和呈递，补体和凝血级联，和IL-17信号通路。此外，蛋白质组学分析表明，将环孢素A药物递送系统（CsA-DDS）植入前房通过抑制角膜移植物和I-CB组织中的免疫反应，明显减轻了角膜移植排斥反应。
结论：结果强调了角膜移植排斥过程中移植物和I-CB组织的眼内免疫受累，进一步表明前房作为其治疗的最佳药物递送部位。
