April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Acid sphingomyelinase activation suppresses the ischemia-induced production of TNF-α in the retina
Author Affiliations & Notes
  • Jie Fan
    Ophthalmology-Storm Eye Inst, Medical Univ of South Carolina, Charleston, SC
  • Oday Alsarraf
    Ophthalmology-Storm Eye Inst, Medical Univ of South Carolina, Charleston, SC
  • Craig E Crosson
    Ophthalmology-Storm Eye Inst, Medical Univ of South Carolina, Charleston, SC
  • Footnotes
    Commercial Relationships Jie Fan, None; Oday Alsarraf, None; Craig Crosson, Lexicon Pharmaceuticals (R)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2664. doi:
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    • Get Citation

      Jie Fan, Oday Alsarraf, Craig E Crosson; Acid sphingomyelinase activation suppresses the ischemia-induced production of TNF-α in the retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2664.

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

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Abstract

Purpose: The pathogenesis of retinal ischemia results from a series of events involving alterations in inflammatory cytokines. Acid sphingomyelinase (ASM) is an important sensor in inflammatory cytokine and apoptotic signaling. It catalyzes the hydrolysis of sphingomyelin to ceramide, a key mediator of cell-stress responses and cell death. However, the role(s) of ASM in retinal neuronal degeneration have not been investigated. The purpose of this study is to investigate whether ASM activation alters the TNF-α levels in the retina after ischemic injury.

Methods: ASM+/-mice and wild-type (WT) littermates were evaluated for the changes in TNF-α, ASM activity and ceramide profiles following retinal ischemia. Retinal ischemic injury was induced by elevating intraocular pressure to 120mmHg for 45 minutes. ASM activity was measured by Amplex Red Spingomyelinase Assay kit. The TNF-α levels were determined by ELISA. Ceramide levels were determined by liquid chromatography-mass spectrometry.

Results: In WT mice, retina ischemia significantly increased the ASM activity by 47±16% at 60 min after the ischemia injury, when compared to contralateral control eyes. In ASM+/- mice, retinal ischemia also slightly increased ASM activity; however, the post ischemia ASM activity was significantly less (40±4%) than that observed in WT mice. The ischemia-induced production of TNF-α increased in a time-dependent manner. 4 hours after ischemia injury, the TNF-α level in ASM+/- retina was 56±5% less than that observed in WT retina. No differences in retinal TNF-α levels were detected between WT and ASM+/- contralateral retinas. The profiles of ceramide displayed significant increases in both WT and ASM+/- ischemic retinas when compares to contralateral retinas at 24 hours. However, there was no difference in ceramide profiles between WT and ASM+/- ischemic retinas.

Conclusions: These results provide evidence that the production of TNF-α after retinal ischemia injury is an early event and that ASM activation suppresses the production of TNF-α. In addition, the inhibition of ASM does not affect the total ceramide production in the retinas. Inhibition of ASM may provide a novel treatment for retinal ischemic disorders.

Keywords: 572 ischemia • 615 neuroprotection • 490 cytokines/chemokines  
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