Myelin-specific Th17 cells induce severe relapsing optic neuritis with irreversible loss of retinal ganglion cells in C57BL/6 mice.
OBJECTIVE
Optic neuritis affects most patients with multiple sclerosis (MS), and current treatments are unreliable. The purpose of this study was to characterize the contribution of Th1 and Th17 cells to the development of optic neuritis.


METHODS
Mice were passively transferred myelin-specific Th1 or Th17 cells to induce experimental autoimmune encephalomyelitis (EAE), a model of neuroautoimmunity. Visual acuity was assessed daily with optokinetic tracking, and 1, 2, and 3 weeks post-induction, optic nerves and retinas were harvested for immunohistochemical analyses.


RESULTS
Passive transfer experimental autoimmune encephalomyelitis elicits acute episodes of asymmetric visual deficits and is exacerbated in Th17-EAE relative to Th1-EAE. The Th17-EAE optic nerves contained more inflammatory infiltrates and an increased neutrophil to macrophage ratio. Significant geographic degeneration of the retinal ganglion cells accompanied Th17-EAE but not Th1.


CONCLUSIONS
Th17-induced transfer EAE recapitulates pathologies observed in MS-associated optic neuritis, namely, monocular episodes of vision loss, optic nerve inflammation, and geographic retinal ganglion cell (RGC) degeneration.
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Chelsea M
CM
Larabee
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Yang
Y
Hu
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Shruti
S
Desai
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Constantin
C
Georgescu
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Jonathan D
JD
Wren
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Robert C
RC
Axtell
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Scott M
SM
Plafker
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D007116:Immunization, Passive; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D009902:Optic Neuritis / Q000276:immunology* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D014792:Visual Acuity / Q000502:physiology