Abstract | BACKGROUND: 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.
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Authors | Dana Morzaev, James D Nicholson, Tomm Caspi, Shirel Weiss, Edith Hochhauser, Nitza Goldenberg-Cohen |
Journal | Clinical & experimental ophthalmology
(Clin Exp Ophthalmol)
2015 Sep-Oct
Vol. 43
Issue 7
Pg. 655-65
ISSN: 1442-9071 [Electronic] Australia |
PMID | 25752496
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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