Effect of fingolimod on the myelin repair and inflammation in focal demyelination of rat optic chiasm

Background and Objective: Fingolimod (FTY720) as a sphingosine 1-phosphate (S1P) receptor agonist, has been introduced as the first oral medicine for relapsing-remitting multiple sclerosis (MS). Besides immunomodulatory role, FTY720 exerts beneficial effects on remyelination process in central nervous system (CNS). In this study, the effect of FTY720 on conductivity of visual signals, myelin repair, glial activation and expression levels of histone deacetylase 1 (HDAC1)/ S1P1R has been evaluated in lysolecithin (LPC)-induced demyelination model in optic chiasm. Materials and Methods: In order to induce demyelination model, LPC (1%, 2 μl) was injected into rat s optic chiasm. Visual evoked potential recording (VEP) was used to measure the latency of visual waves. The extent of demyelination area and levels of glial activation were assessed using immunostaining. Gene expression analysis was performed to evaluate the expression levels of HDAC1, S1P1R, Olig2 and MBP in the optic chiasm. Findings: Analysis of electrophysiological data showed that injection of LPC increased the latency of visual signals and application of FTY720 significantly improved the functional recovery of visual pathway and alleviated the levels of glial activation in the optic chiasm. FTY720 enhanced the myelin repair and upregulated the expression levels of Olig2 and MBP. Additionally, the expression levels of HDAC1/ S1P1R were significantly reduced in animals treated with FTY720. Conclusion: Cumulatively, the results of the present study demonstrate that FTY720 application improves the functional recovery of optic pathway through enhancement of remyelination, alleviation of glial activation and downregulation of S1P1R/HDAC1 .

کلیدواژه ها:

Fingolimod ، Lysolecithin ، Visual evoked potential recording ، Remyelination ، Histone deacetylase ، Optic chiasm