title: Neuroprotective effects of recombinant T-cell receptor ligand in autoimmune optic neuritis in HLA-DR2 mice.
abstract: OBJECTIVE
  Optic neuritis (ON) is a condition involving primary inflammation, demyelination, and axonal injury in the optic nerve and leads to apoptotic retinal ganglion cell (RGC) death, which contributes to the persistence of visual loss. Currently, ON has no effective treatment. The goal was to determine the effectiveness of immunotherapy with recombinant T-cell receptor ligand (RTL) in preventing ON in humanized HLA-DR2 transgenic mice.
  
  
  METHODS
  Experimental autoimmune encephalomyelitis (EAE) was induced with myelin oligodendrocyte glycoprotein in humanized HLA-DR2 (DRβ1*1501) transgenic mice. Five consecutive doses of RTL342M were administrated at the onset of ON. The development of autoimmune ON was assessed by histopathology at different time points. The levels of myelin loss, axonal loss, and RGC damage were examined by immunofluorescence.
  
  
  RESULTS
  HLA-DR2 mice developed chronic ON 2 days before EAE characterized by progressive neurodegeneration in both organs. RTL342M significantly suppressed inflammation in the optic nerve and spinal cord and provided protection for at least 30 days. Examination of myelin loss showed a marked suppression of demyelination and an increase in myelin recovery in the optic nerve. Moreover, RTL342M treatment revealed a neuroprotective effect on optic nerve axons and RGCs in retinas at postimmunization (PI) day 62.
  
  
  CONCLUSIONS
  RTL342M suppressed clinical and histologic signs of EAE/ON by preventing the recruitment of inflammatory cells into the optic nerve and showed neuroprotective effects against ON. However, to achieve full therapeutic benefit, more doses may be needed. These findings suggest a possible clinical application of this novel class of T-cell-tolerizing drugs for patients with optic neuritis.
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA. adamusg@ohsu.edu
authors.forename: Grazyna
authors.initials: G
authors.lastname: Adamus
authors.forename: Lori
authors.initials: L
authors.lastname: Brown
authors.forename: Shayne
authors.initials: S
authors.lastname: Andrew
authors.forename: Roberto
authors.initials: R
authors.lastname: Meza-Romero
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Burrows
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins / Q000633:toxicity; D059811:HLA-DRB1 Chains / Q000235:genetics; D007167:Immunotherapy; D008024:Ligands; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009902:Optic Neuritis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000633:toxicity; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use; D012165:Retinal Ganglion Cells / Q000473:pathology; D019076:Transgenes
chemical_list: D006023:Glycoproteins; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D008024:Ligands; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C571058:RTL342M protein, mouse; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C445081:myelin oligodendrocyte glycoprotein (35-55)