RGD Reference Report - Neuroprotective effects of recombinant T-cell receptor ligand in autoimmune optic neuritis in HLA-DR2 mice. - Rat Genome Database

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Neuroprotective effects of recombinant T-cell receptor ligand in autoimmune optic neuritis in HLA-DR2 mice.

Authors: Adamus, G  Brown, L  Andrew, S  Meza-Romero, R  Burrows, GG  Vandenbark, AA 
Citation: Adamus G, etal., Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):406-12. doi: 10.1167/iovs.11-8419.
RGD ID: 7365050
Pubmed: PMID:22167100   (View Abstract at PubMed)
PMCID: PMC3292374   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.11-8419   (Journal Full-text)

PURPOSE: 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 (DRbeta1*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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
optic neuritis  ISOHLA-DRB1 (Homo sapiens)7365050; 7365050associated with Encephalomyelitis more ...RGD 
optic neuritis  IMP 7365050associated with Encephalomyelitis more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Db1  (RT1 class II, locus Db1)

Genes (Mus musculus)
H2-Eb1  (histocompatibility 2, class II antigen E beta)

Genes (Homo sapiens)
HLA-DRB1  (major histocompatibility complex, class II, DR beta 1)


Additional Information