Neuroprotective Effects of Fingolimod in a Cellular Model of Optic Neuritis

被引:6
作者
Candadai, Amritha A. [1 ,2 ,3 ]
Liu, Fang [1 ,2 ,3 ]
Verma, Arti [1 ,2 ]
Adil, Mir S. [1 ,2 ]
Alfarhan, Moaddey [1 ,2 ,3 ]
Fagan, Susan C. [1 ,2 ]
Somanath, Payaningal R. [1 ,2 ]
Narayanan, S. Priya [1 ,2 ,3 ]
机构
[1] Univ Georgia, Coll Pharm, Clin & Expt Therapeut Program, Augusta, GA 30912 USA
[2] Charlie Norwood VA Med Ctr, Augusta, GA 30912 USA
[3] Augusta Univ, Culver Vis Discovery Inst, Augusta, GA 30912 USA
关键词
optic neuritis; multiple sclerosis; oxidative stress; neuroprotection; fingolimod; NECROSIS-FACTOR-ALPHA; MULTIPLE-SCLEROSIS; OXIDATIVE STRESS; MICROGLIAL ACTIVATION; RETINAL NEURONS; FTY720; PROTEIN; CELLS; IMMUNOSUPPRESSANT; NEUROINFLAMMATION;
D O I
10.3390/cells10112938
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Visual dysfunction resulting from optic neuritis (ON) is one of the most common clinical manifestations of multiple sclerosis (MS), characterized by loss of retinal ganglion cells, thinning of the nerve fiber layer, and inflammation to the optic nerve. Current treatments available for ON or MS are only partially effective, specifically target the inflammatory phase, and have limited effects on long-term disability. Fingolimod (FTY) is an FDA-approved immunomodulatory agent for MS therapy. The objective of the current study was to evaluate the neuroprotective properties of FTY in the cellular model of ON-associated neuronal damage. R28 retinal neuronal cell damage was induced through treatment with tumor necrosis factor-alpha (TNF alpha). In our cell viability analysis, FTY treatment showed significantly reduced TNF alpha-induced neuronal death. Treatment with FTY attenuated the TNF alpha-induced changes in cell survival and cell stress signaling molecules. Furthermore, immunofluorescence studies performed using various markers indicated that FTY treatment protects the R28 cells against the TNF alpha-induced neurodegenerative changes by suppressing reactive oxygen species generation and promoting the expression of neuronal markers. In conclusion, our study suggests neuroprotective effects of FTY in an in vitro model of optic neuritis.
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页数:16
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