TY - JOUR
T1 - TNF-α is critical for ischemia-induced leukostasis, but not retinal neovascularization nor VEGF-induced leakage
AU - Vinores, Stanley A.
AU - Xiao, Wei Hong
AU - Shen, Ji Kui
AU - Campochiaro, Peter A.
N1 - Funding Information:
Supported by EY12609, and core grant P30EY1765 from the NEI; an unrestricted grant from Research to Prevent Blindness, Inc; Dr. and Mrs. William Lake.
PY - 2007/1
Y1 - 2007/1
N2 - Vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) show significant overlap with regard to their effects in the eye. It has been postulated that VEGF-induced leukostasis, breakdown of the blood-retinal barrier, and ischemia-induced retinal neovascularization may be mediated, at least in part, through TNF-α. In this study, we used mice deficient in TNF-α to test our hypothesis. Compared to wild type mice, TNF-α-deficient mice showed an 80% reduction in leukocyte accumulation in retinal vessels after intravitreous injection of VEGF, and 100% reductions after intravitreous injections of interleukin-1β (IL-1β) or platelet-activating factor (PAF). The increase in retinal vascular permeability induced by injection of PAF was significantly reduced in mice lacking TNF-α, but VEGF- and IL-1β-induced leakage was unaffected. Compared to wild type mice with oxygen-induced ischemic retinopathy, TNF-α-deficient mice with ischemic retinopathy showed significantly reduced leukostasis and mild reduction in vascular leakage, but no significant difference in retinal neovascularization. These data suggest that TNF-α mediates VEGF-, IL-1β-, and PAF-induced leukostasis and vascular leakage mediated by PAF, but not leakage caused by VEGF or IL-1β. Ischemia-induced retinal neovascularization, which has previously been shown to require VEGF, does not require TNF-α and is unaffected by attenuation of leukostasis.
AB - Vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α) show significant overlap with regard to their effects in the eye. It has been postulated that VEGF-induced leukostasis, breakdown of the blood-retinal barrier, and ischemia-induced retinal neovascularization may be mediated, at least in part, through TNF-α. In this study, we used mice deficient in TNF-α to test our hypothesis. Compared to wild type mice, TNF-α-deficient mice showed an 80% reduction in leukocyte accumulation in retinal vessels after intravitreous injection of VEGF, and 100% reductions after intravitreous injections of interleukin-1β (IL-1β) or platelet-activating factor (PAF). The increase in retinal vascular permeability induced by injection of PAF was significantly reduced in mice lacking TNF-α, but VEGF- and IL-1β-induced leakage was unaffected. Compared to wild type mice with oxygen-induced ischemic retinopathy, TNF-α-deficient mice with ischemic retinopathy showed significantly reduced leukostasis and mild reduction in vascular leakage, but no significant difference in retinal neovascularization. These data suggest that TNF-α mediates VEGF-, IL-1β-, and PAF-induced leukostasis and vascular leakage mediated by PAF, but not leakage caused by VEGF or IL-1β. Ischemia-induced retinal neovascularization, which has previously been shown to require VEGF, does not require TNF-α and is unaffected by attenuation of leukostasis.
KW - Blood-retinal barrier
KW - Interleukin-1β
KW - Leukostasis
KW - Platelet activating factor
KW - Retinal neovascularization
KW - Tumor necrosis factor-α
KW - Vascular endothelial growth factor
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U2 - 10.1016/j.jneuroim.2006.09.015
DO - 10.1016/j.jneuroim.2006.09.015
M3 - Article
C2 - 17107717
AN - SCOPUS:33846016638
SN - 0165-5728
VL - 182
SP - 73
EP - 79
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -