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Toll-like receptor-4 knockout mice are more resistant to optic nerve crush damage than wild-type mice.

AbstractBACKGROUND:
This study aims to investigate the role of the inflammatory response following optic nerve crush (ONC) in knockout mice for the toll-like receptor-4 gene (TLR4-/-) compared to wild-type (WT) mice.
METHODS:
ONC was induced in TLR4-/- and C57BL6 WT mice. Histological sections of the retina and optic nerve were analysed on days 1, 3 or 21 after injury. Molecular analysis with real-time quantitative polymerase chain reaction was used to study the expression of CD45, tumour necrosis-alpha (TNF-α) and glial fibrillary acidic protein, as well as retinal ganglion cell (RGC) markers THY-1 and Brn3b.
RESULTS:
There was a 25.5% and 38% loss in the RGC layer of the ONC-injured eyes of the TLR4-/- and the WT mice, respectively (with 27% and 9% of the remaining cells positive for Brn3a, respectively). Mean levels of Thy-1 and Brn3b were higher in the TLR4-/- mice. CD45 and Iba1 staining revealed infiltration of inflammatory cells into the injured nerve and retina in both groups. Molecular analysis of the optic nerve on day 1 showed increased TNF-α expression and reduced CD45 and GFAP expression; on day 3, CD45 reverted to baseline but GFAP remained low; on day 21, all 3 markers were at baseline in the TLR4-/- group and decreased in the WT group.
CONCLUSION:
Inflammation plays a major role in the response to ONC injury. Reduced levels of inflammation are associated with improved RGC preservation. The increase in TNF-α and reduction in CD45 in both TLR4-/- and WT mice may indicate the presence of an alternative pathway for induction of RGC death.
AuthorsDana Morzaev, James D Nicholson, Tomm Caspi, Shirel Weiss, Edith Hochhauser, Nitza Goldenberg-Cohen
JournalClinical & experimental ophthalmology (Clin Exp Ophthalmol) 2015 Sep-Oct Vol. 43 Issue 7 Pg. 655-65 ISSN: 1442-9071 [Electronic] Australia
PMID25752496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 Royal Australian and New Zealand College of Ophthalmologists.
Chemical References
  • Glial Fibrillary Acidic Protein
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Pou4f2 protein, mouse
  • RNA, Messenger
  • Thy-1 Antigens
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factor Brn-3B
  • Tumor Necrosis Factor-alpha
  • glial fibrillary astrocytic protein, mouse
  • Leukocyte Common Antigens
  • Ptprc protein, mouse
Topics
  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein
  • Homeodomain Proteins (metabolism)
  • Leukocyte Common Antigens (genetics, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Crush
  • Nerve Tissue Proteins (genetics, metabolism)
  • Optic Nerve Injuries (genetics, metabolism, pathology)
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Retinal Ganglion Cells (metabolism, pathology)
  • Thy-1 Antigens (metabolism)
  • Toll-Like Receptor 4 (physiology)
  • Transcription Factor Brn-3B (metabolism)
  • Tumor Necrosis Factor-alpha (genetics, metabolism)

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