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Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury.
- Source :
-
Molecular vision [Mol Vis] 2010 Sep 30; Vol. 16, pp. 1907-12. Date of Electronic Publication: 2010 Sep 30. - Publication Year :
- 2010
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Abstract
- Purpose: We investigated whether retinal ischemia and inflammation produced by raising the intraocular pressure above normal systolic levels differs in mice that lack a functional toll-like receptor 4 (Tlr4) signaling pathway.<br />Methods: In this work we used the murine strain B6.B10ScN-Tlr4(lps-del)/JthJ, which does not express functional Tlr4. C57BL/6J was considered as the control. We induced retinal ischemia by unilateral elevation of intraocular pressure for 1 h by direct corneal cannulation. The changes in expression of proinflammatory genes 24 h postreperfusion were assessed by quantitative PCR. Corresponding changes in protein abundances were analyzed by western blot and immunohistochemistry. Cell death was evaluated by direct counting of neurons in the ganglion cell layer of flat-mounted retinas seven days postreperfusion.<br />Results: We showed that Tlr4-deficient mice display significantly reduced expression of proinflammatory genes, including RelA, tumor necrosis factor (Thf), interleukin 6 (Il6), chemokine (C-C motif) ligand 2 (Ccl2), chemokine (C-C motif) ligand 5 (Ccl5), chemokine (C-X-C motif) ligand 10 (Cxcl10), Cybb, nitric oxide synthase 2 (Nos2), and intercellular adhesion molecule 1 (Icam1) 24 h after reperfusion. The mice that lacked Tlr4 showed significantly increased survival of neurons in the ganglion cell layer following ischemic injury, as compared to wild-type controls.<br />Conclusions: Our results indicate that Tlr4 signaling is involved in retinal damage and inflammation triggered by ischemic injury.
- Subjects :
- Animals
Cell Survival
Cytoprotection
Inflammation complications
Inflammation pathology
Inflammation Mediators metabolism
Mice
Mice, Inbred C57BL
Reperfusion Injury complications
Reperfusion Injury pathology
Retinal Neurons metabolism
Retinal Neurons pathology
Signal Transduction
Toll-Like Receptor 4 deficiency
Reperfusion Injury metabolism
Retina metabolism
Retina pathology
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 16
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 21031135