Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival.
Development and Effects of FTY720 Ophthalmic Solution on Corneal Allograft Survival.
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FTY720滴眼液的研制及其对同种异体角膜移植物存活的影响
DOI：
10.1038/srep16468
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发表时间：
2015-11-12
影响因子：
4.6
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Liu Z;Lin H;Huang C;Chen W;Xiang W;Geng Y;Chen W
芬戈莫德 (FTY720) 是一类新型 1-磷酸鞘氨醇受体调节剂，引起了眼科医生的特别关注，特别是考虑到口服 FTY720 已被证明可以有效治疗动物模型中的角膜移植排斥反应。然而，尚无研究检验 FTY720 作为滴眼液在高风险角膜排斥模型中减少角膜排斥反应的性能，并且 FTY720 滴眼液的稳定性和眼部刺激特征也未知。因此，我们开发了 0.1%、0.2% 和 0.5% FTY720 滴眼液，并利用高效液相色谱法评估了它们在各种储存条件下的化学稳定性。为了研究FTY720眼药水的眼部刺激性，对新西兰白化兔进行了Draize试验。此外，还使用经典、完善的大鼠同种异体穿透性角膜移植模型来研究所测试的 FTY720 眼科溶液的抗排斥功效。我们发现无刺激性的0.5%FTY720滴眼液可以延长大鼠同种异体角膜的存活时间，效果显着，可持续1个月左右。此外，任何类型的FTY720滴眼液在三个月内均未发生明显的浓度变化。这些结果揭示了 FTY720 眼科溶液的关键特征，并值得进一步研究和优化 FTY720 在角膜移植术后抗排斥治疗中的应用。
Fingolimod (FTY720), a novel class of sphingosine 1-phosphate receptor modulators, has received special interest among ophthalmologists, particularly given that oral administration of FTY720 has proven to effectively treat corneal graft rejection in animal models. However, no studies have examined the performance of FTY720 as an ophthalmic solution in reducing corneal rejection in high-risk corneal rejection models and the stability and ocular irritation profile of FTY720 ophthalmic solution are also unknown. Thus, we developed 0.1%, 0.2% and 0.5% FTY720 ophthalmic solutions and evaluated their chemical stabilities under various storage conditions with high- performance liquid chromatography. To investigate the ocular irritancy of the FTY720 ophthalmic solution, New Zealand albino rabbits were subjected to the Draize test. Furthermore, classic, well-established rat allogenic penetrating keratoplasty models were used to investigate the anti-rejection efficacy of the tested FTY720 ophthalmic solutions. We found that the non-irritating 0.5% FTY720 ophthalmic solution could prolong corneal allograft survival in rats with significant efficacy for about one month. Furthermore, no significant concentration changes occurred in any of the types of FTY720 ophthalmic solutions within three months. These results revealed crucial profiles of FTY720 ophthalmic solutions and warrant further investigation and optimization of FTY720 in the anti-rejection therapy after keratoplasty.