Trufanov S V, Subbot A M, Malozhen S A, Krakhmaleva D A
Research Institute of Eye Diseases, 11 A, B, Rossolimo St., Moscow, Russian Federation, 119021.
Vestn Oftalmol. 2016;132(5):117-124. doi: 10.17116/oftalma20161325117-124.
Transplantation of donated cornea is a radical and pathogenetically oriented measure of rehabilitation for patients with corneal blindness. Unlike other transplantation surgeries, keratoplasty is usually done without tissue typing and systemic immunosuppression. Even so, in the absence of risk factors, grafts can remain clear in as many as 90% of cases. The phenomenon is explained by immune privilege of the cornea. The hypothesis of immune privilege comprises several interrelated mechanisms that ensure long-lasting transparency of the graft. These include transfer limits of immunogenic stimuli to peripheral lymphoid tissues, deviation of the immune response, and neutralization of immune effector elements within the host-graft interface by immunosuppressive ocular environment. A change in any of the said components leads to loss of the immune-privilege status of the cornea, thus, significantly increasing the risk of graft rejection. We know several stages of the response activation cascade in graft rejection that can be influenced therapeutically, namely, antigen absorption, processing, and presentation as well as T-cell expansion and cellular inflow to the eye. The first two stages take place in the eye itself and are susceptible to instillation drugs and gene therapy. New highly selective medications aimed at specific signals from the immune cells and their pathways may be able to help restore the immune privilege of the cornea and improve the results of optical and reconstructive surgeries in high-risk patients.
捐献角膜移植是针对角膜盲患者的一种根治性且基于发病机制的康复措施。与其他移植手术不同,角膜移植通常在不进行组织配型和全身免疫抑制的情况下进行。即便如此,在没有危险因素的情况下,多达90%的病例中移植物可保持透明。这种现象可由角膜的免疫赦免来解释。免疫赦免假说包含几个相互关联的机制,这些机制可确保移植物长期保持透明。其中包括免疫原性刺激向周围淋巴组织的传递限制、免疫反应的偏离,以及免疫抑制性眼内环境对宿主-移植物界面内免疫效应元件的中和作用。上述任何一个成分发生变化都会导致角膜免疫赦免状态的丧失,从而显著增加移植物排斥的风险。我们了解移植物排斥反应激活级联的几个阶段,这些阶段可通过治疗加以影响,即抗原吸收、加工和呈递,以及T细胞扩增和细胞流入眼内。前两个阶段发生在眼内本身,易受滴眼药物和基因治疗的影响。针对免疫细胞及其信号通路的特定信号的新型高选择性药物或许能够帮助恢复角膜的免疫赦免,并改善高危患者的眼科光学和重建手术效果。