title: Deleterious role of TNF-alpha in retinal ischemia-reperfusion injury.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF)-alpha is a mediator of neuronal cell death and survival in ischemia-reperfusion injury. This study was conducted to further elucidate the role of TNF-alpha and its receptor in an in vivo model of retinal ischemia-reperfusion injury by investigating its effects on retinal histopathology and function.
  
  
  METHODS
  Retinal ischemia-reperfusion injury was performed on p55 and p75 knockout (KO) mice and Sprague-Dawley rats using the high intraocular pressure
  
  
  METHODS
  The temporal expression of TNF-alpha was ascertained with immunohistochemical staining. Separate rats received intravitreal recombinant TNF-alpha or neutralizing antibody before or after ischemia. TUNEL labeling was performed to assess for cell death, and electroretinography was performed to assess function.
  
  
  RESULTS
  TNF-alpha expression peaked at 12 to 24 hours after ischemia-reperfusion injury. TUNEL staining was diminished after intravitreal TNF-alpha antibody. Both transgenic KOs demonstrated significantly less functional impairment. Rats receiving recombinant TNF-alpha 48 hours after ischemia showed exaggerated functional impairment. Animals treated with TNF-alpha antibody before ischemia displayed significant functional improvement.
  
  
  CONCLUSIONS
  TNF-alpha plays a largely deleterious role in ischemia-reperfusion injury in an in vivo model of retinal injury. Direct neutralization of this cytokine partially preserves retinal function. The diverse characteristics of TNF-alpha are attributed in part to the timing of its expression after injury. TNF-alpha receptor expression and function, along with combination treatments targeting death receptor-mediated apoptosis, should be further explored to develop neuroprotective therapeutic strategies for acute retinal ischemic disorders.
authors.affiliation: Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York11203, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Berger
authors.forename: Sean I
authors.initials: SI
authors.lastname: Savitz
authors.forename: Sheetal
authors.initials: S
authors.lastname: Nijhawan
authors.forename: Manjeet
authors.initials: M
authors.lastname: Singh
authors.forename: Joel
authors.initials: J
authors.lastname: David
authors.forename: Pearl S
authors.initials: PS
authors.lastname: Rosenbaum
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D017209:Apoptosis; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012164:Retinal Diseases / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000502:physiology*; D014822:Vitreous Body
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha