Klebe Sonja, Coster Douglas J, Williams Keryn A
Department of Ophthalmology, Flinders University, Adelaide, Australia.
Curr Opin Organ Transplant. 2009 Feb;14(1):4-9. doi: 10.1097/MOT.0b013e32831af1d7.
Corneal transplantation is successful in the short-term, but the long-term prognosis has not improved over the past 20 years. Here, we review recent findings that may contribute to improved corneal allograft survival.
A better understanding of the molecular pathways affecting corneal graft survival has led to more targeted approaches to immune modulation. Costimulatory molecule blockade, inhibition of chemokine-chemokine receptor interactions, modulation of apoptotic pathways, and reduction of corneal neovascularization and lymphangiogenesis have been shown to prolong corneal graft survival in animal models. Conventional immunosuppressive drugs have been tested in new combinations and formulations with some success. Two randomized prospective clinical trials in clinical penetrating corneal transplantation have been reported, but there remains little evidence on the long-term outcomes of the newer lamellar corneal graft procedures.
New approaches to reducing the impact of rejection on corneal graft survival have focussed on topical rather than systemic therapies, and on component corneal transplantation. The most successful experimental strategies have been those in which more than one pathway has been targeted; it now seems likely that to improve clinical allograft survival, simultaneous modulation of multiple axes of the rejection process will be necessary.
角膜移植在短期内是成功的,但在过去20年里长期预后并未得到改善。在此,我们综述近期可能有助于提高角膜移植存活率的研究发现。
对影响角膜移植存活的分子途径有了更好的理解,从而产生了更具针对性的免疫调节方法。在动物模型中,共刺激分子阻断、趋化因子 - 趋化因子受体相互作用的抑制、凋亡途径的调节以及角膜新生血管化和淋巴管生成的减少已被证明可延长角膜移植的存活时间。传统免疫抑制药物已进行新的联合和剂型测试并取得了一些成功。已有两项关于临床穿透性角膜移植的随机前瞻性临床试验报告,但关于新型板层角膜移植手术的长期结果仍缺乏证据。
减少排斥反应对角膜移植存活影响的新方法集中在局部而非全身治疗以及成分角膜移植上。最成功的实验策略是那些针对多个途径的策略;现在看来,要提高临床移植存活率,同时调节排斥过程的多个轴可能是必要的。