Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan.
J Neuroophthalmol. 2013 Jun;33(2):143-8. doi: 10.1097/WNO.0b013e31828ea2fc.
Fingolimod is an immunomodulating agent that has been approved for the treatment of multiple sclerosis. Fingolimod-phosphate is an antagonist of sphingosine-1-phosphate receptor and known to act by preventing infiltration of autoreactive lymphocytes into the central nervous system. In this study, we investigated whether fingolimod prevents experimental autoimmune optic neuritis (EAON).
EAON was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein-derived peptide 35-55 (MOG-p). After MOG-p immunization, fingolimod was administered intragastrically from day 1 (entire phase study) or from day 9 (effector phase study) until day 35. Visual acuity of the mice was measured using OptoMotry on days 7, 14, 21, 28, and 35 after immunization. On day 35 after immunization, the mice were killed and eyes and entire length of the optic nerves were submitted for histopathologic evaluation.
In the positive control group, visual acuity decreased markedly from approximately day 14 after immunization, reaching a nadir on day 21. In the fingolimod-treated groups in both entire phase and effector phase studies, there was only minimal decline in visual acuity on day 14 after immunization, and mild deterioration on day 21, followed by recovery. Histopathologic study showed that fingolimod given throughout the entire phase or only from the effector phase suppressed murine EAON. Immunohistochemical study for neurofilament demonstrated no irregularity of the linear structure of the optic nerve in the fingolimod-treated mice compared with the positive control group.
Fingolimod ameliorated EAON even when started after optic neuritis had developed. Further study is warranted to examine whether these findings are applicable to human disease.
芬戈莫德是一种免疫调节剂，已被批准用于治疗多发性硬化症。芬戈莫德磷酸盐是一种鞘氨醇-1-磷酸受体拮抗剂，已知通过阻止自身反应性淋巴细胞浸润中枢神经系统而起作用。在这项研究中，我们研究了芬戈莫德是否可预防实验性自身免疫性视神经炎（EAON）。
通过用髓鞘少突胶质细胞糖蛋白衍生肽 35-55（MOG-p）免疫 C57BL/6 小鼠诱导 EAON。在 MOG-p 免疫后，从第 1 天（整个阶段研究）或第 9 天（效应阶段研究）开始，每天经胃内给药至第 35 天。在免疫后第 7、14、21、28 和 35 天使用 OptoMotry 测量小鼠的视力。在免疫后第 35 天处死小鼠，对眼睛和整个视神经长度进行组织病理学评估。
在阳性对照组中，从免疫后约第 14 天开始，视力明显下降，在第 21 天达到最低点。在整个阶段和效应阶段研究中，芬戈莫德治疗组在免疫后第 14 天仅有轻微的视力下降，第 21 天略有恶化，随后恢复。组织病理学研究表明，在整个阶段或仅在效应阶段给予芬戈莫德可抑制小鼠的 EAON。与阳性对照组相比，用免疫组织化学研究神经丝显示，芬戈莫德治疗组小鼠视神经的线性结构没有不规则。
即使在视神经炎发生后开始给予芬戈莫德，也可改善 EAON。需要进一步研究以检查这些发现是否适用于人类疾病。
