Toll‐like receptor‐4 knockout mice are more resistant to optic nerve crush damage than wild‐type mice. (13th May 2015)

• Record Type: Journal Article
• Authors: Morzaev, Dana; Nicholson, James D; Caspi, Tomm; Weiss, Shirel; Hochhauser, Edith; Goldenberg‐Cohen, Nitza
• Is Part Of: Clinical & experimental ophthalmology. Volume 43:Number 7(2015)
• Page Start: 655
• Page End: 665
• Publication Date: 2015-05-13
• Subjects: Ophthalmology -- Periodicals; 617.7
• DOI: 10.1111/ceo.12521
• Languages: English
• ISSNs: 1442-6404

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="ceo12521-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="ceo12521-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="ceo12521-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="ceo12521-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>