Song Yao-Wen, Pan Zhi-Qiang
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing 100730, China.
Int J Ophthalmol. 2019 Feb 18;12(2):324-332. doi: 10.18240/ijo.2019.02.21. eCollection 2019.
Donor cornea shortage is a primary hurdle in the development of corneal transplantation. Of all species, porcine corneas are the ideal transplantation material for humans. However, the xenoimmune rejection induced by porcine corneal xenotransplantation compromises surgical efficacy. Although the binding of IgM/IgG in human serum to a genetically modified porcine cornea is significantly weaker than that of the wild type (WT), genetically modified porcine corneas do not display a prolonged graft survival time . Conversely, costimulatory blockade drugs, such as anti-CD40 antibodies, can reduce the xenoimmune response and prolong graft survival time in animal experiments. Moreover, porcine endothelial grafts can survive for more than 6mo with only the subconjunctival injection of a steroid-based immunosuppressants regime; therefore, they show great value for treating corneal endothelial disease. In addition, zoonotic transmission is a primary concern of xenotransplantation. Porcine endogenous retrovirus (PERV) is the most significant virus assessed by ophthalmologists. PERV integrates into the porcine genome and infects human cells . Fortunately, no evidence from studies has yet shown that PERV can be transmitted to hosts.
供体角膜短缺是角膜移植发展的主要障碍。在所有物种中,猪角膜是人类理想的移植材料。然而,猪角膜异种移植引发的异种免疫排斥会影响手术效果。尽管人血清中IgM/IgG与基因编辑猪角膜的结合明显弱于野生型(WT),但基因编辑猪角膜的移植存活时间并未延长。相反,共刺激阻断药物,如抗CD40抗体,在动物实验中可减少异种免疫反应并延长移植存活时间。此外,仅通过结膜下注射基于类固醇的免疫抑制剂方案,猪内皮移植物就能存活超过6个月;因此,它们在治疗角膜内皮疾病方面具有很大价值。此外,人畜共患病传播是异种移植的主要担忧。猪内源性逆转录病毒(PERV)是眼科医生评估的最重要病毒。PERV整合到猪基因组中并感染人类细胞。幸运的是,尚无研究证据表明PERV可传播给宿主。