June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The Role Of Tlr4 In Retinal Ganglion Cell Death After Ischemia
Author Affiliations & Notes
  • Andrea Rachelle Santos
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Galina Dvoriantchikova
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Eleut Hernandez
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, FL
  • Dmitry Ivanov
    Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, FL
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1777. doi:
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      Andrea Rachelle Santos, Galina Dvoriantchikova, Eleut Hernandez, Dmitry Ivanov; The Role Of Tlr4 In Retinal Ganglion Cell Death After Ischemia. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1777.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Increasing experimental evidence suggests an important role for Toll-like receptor 4 (Tlr4) in retinal ischemia-reperfusion (IR) injury. The specific role of neuronal Tlr4 after ischemia recently began to unravel when the pivotal role of neuronal Tlr4 in ischemic brain injury was shown. Since mechanisms of neuronal death after ischemia share similarities with the central nervous system (CNS), we suggest that Tlr4 could play a detrimental role in retinal ganglion cell (RGC) death after ischemia.

Methods: Wild type (WT) or Tlr4-deficient animals were used. RGCs isolated by immunopanning were exposed to oxygen and glucose deprivation (OGD) as well as were treated with Tlr4 ligands such as Hsp70 and LPS. The expression level of Tlr4 was evaluated by quantitative PCR and immunocytochemistry. The survival level of RGCs was assessed using Annexin V/PI. The level of reactive oxygen species (ROS) generated was assayed by dihydroethidium (DHE). The NAD(P)H oxidase inhibitors were then tested to determine if it altered the production of ROS within the RGCs and promoted cell survival.

Results: We report that RGCs expressed Tlr4, and the level of Tlr4 is increased in neurons after ischemia. Quantification of cell death showed that RGCs from Tlr4 deficient mice were significantly more resistant to OGD-induced cell death as compared to neurons from WT mice. Importantly, we observed a significantly increased level of RGC death after treatment by Tlr4 ligands. To further elucidate a mechanism of cell death, we tested whether neuronal Tlr4 can regulate oxidative stress in vitro. We detected that Tlr4 mediates ROS production after ischemia and Tlr4 ligand treatment. At the same time, the NAD(P)H oxidase inhibitors decreased the burst stimulated by the OGD or Tlr4 ligand treatment, which was associated with a decreased level of RGC death.

Conclusions: Our findings suggest that RGCs express Tlr4 under normal conditions and after ischemia. Our data supports the hypothesis that ischemia-induced activation of neuronal Tlr4 increases ROS production in RGCs via NAD(P)H oxidase activity that mediates RGC injury.

Keywords: 695 retinal degenerations: cell biology • 572 ischemia  
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