RGD Reference Report - Stimulation of axon regeneration in the mature optic nerve by intravitreal application of the toll-like receptor 2 agonist Pam3Cys. - Rat Genome Database

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Stimulation of axon regeneration in the mature optic nerve by intravitreal application of the toll-like receptor 2 agonist Pam3Cys.

Authors: Hauk, Thomas G  Leibinger, Marco  Müller, Adrienne  Andreadaki, Anastasia  Knippschild, Uwe  Fischer, Dietmar 
Citation: Hauk TG, etal., Invest Ophthalmol Vis Sci. 2010 Jan;51(1):459-64. doi: 10.1167/iovs.09-4203. Epub 2009 Aug 6.
RGD ID: 597538516
Pubmed: PMID:19661221   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.09-4203   (Journal Full-text)


PURPOSE: After injury of the optic nerve, mature retinal ganglion cells (RGCs) are normally unable to regenerate axons and undergo apoptosis. However, inflammatory stimulation in the eye induced by the release of beta/gamma-crystallins from the injured lens or intravitreal zymosan injection transforms RGCs into an active regenerative state, protecting these neurons from cell death and allowing them to regenerate axons back into the optic nerve.
METHODS: The authors tested whether intravitreal application of the selective, water-soluble, toll-like receptor 2 agonist Pam(3)Cys can delay axotomized RGC cell death and stimulate the regeneration of axons using an in vitro and in vivo paradigm.
RESULTS: Intravitreal injection of Pam(3)Cys, as lens injury (LI), induced the upregulation of ciliary neurotrophic factor and glial fibrillary acidic protein expression in retinal glia accompanied by the activation of the JAK/STAT3 pathway in RGCs. As a consequence, RGCs switched to a regenerative state, indicated by a significant upregulation of GAP43 expression and increased neurite outgrowth of RGCs in culture. Repeated intravitreal Pam(3)Cys application in vivo induced neuroprotective effects and caused stronger axon regeneration in the injured optic nerve than observed after LI.
CONCLUSIONS: Pam(3)Cys may be a suitable agent for stimulating CNS regeneration.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TLR2HumanOptic Nerve Injuries treatmentISOTlr2 (Rattus norvegicus) RGD 
Tlr2RatOptic Nerve Injuries treatmentIDA  RGD 
Tlr2MouseOptic Nerve Injuries treatmentISOTlr2 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tlr2Ratpositive regulation of neuron projection development  IDA  RGD 
Tlr2Ratpositive regulation of receptor signaling pathway via JAK-STAT  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr2  (toll-like receptor 2)

Genes (Mus musculus)
Tlr2  (toll-like receptor 2)

Genes (Homo sapiens)
TLR2  (toll like receptor 2)


Additional Information