Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury

Galina Dvoriantchikova, David J. Barakat, Eleut Hernandez, Valery I Shestopalov, Dmitry V Ivanov

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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. Methods: In this work we used the murine strain B6.B10ScN-Tlr4lps-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. 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. Conclusions: Our results indicate that Tlr4 signaling is involved in retinal damage and inflammation triggered by ischemic injury.

Original languageEnglish
Pages (from-to)1907-1912
Number of pages6
JournalMolecular Vision
Volume16
StatePublished - Nov 18 2010

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Toll-Like Receptor 4
Reperfusion Injury
Intraocular Pressure
Ganglia
Ischemia
Chemokine CXCL10
Inflammation
Gene Expression
Neurons
CC Chemokines
Chemokine CCL2
Wounds and Injuries
Intercellular Adhesion Molecule-1
Nitric Oxide Synthase
Catheterization
Reperfusion
Retina
Interleukin-6
Cell Death
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Ophthalmology

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Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury. / Dvoriantchikova, Galina; Barakat, David J.; Hernandez, Eleut; Shestopalov, Valery I; Ivanov, Dmitry V.

In: Molecular Vision, Vol. 16, 18.11.2010, p. 1907-1912.

Research output: Contribution to journalArticle

Dvoriantchikova, G, Barakat, DJ, Hernandez, E, Shestopalov, VI & Ivanov, DV 2010, 'Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury', Molecular Vision, vol. 16, pp. 1907-1912.
Dvoriantchikova, Galina ; Barakat, David J. ; Hernandez, Eleut ; Shestopalov, Valery I ; Ivanov, Dmitry V. / Toll-like receptor 4 contributes to retinal ischemia/reperfusion injury. In: Molecular Vision. 2010 ; Vol. 16. pp. 1907-1912.
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