Tumor Necrosis Factor-α Mediates Photoreceptor Death in a Rodent Model of Retinal Detachment

摘要: Photoreceptors are vulnerable in several retinal disorders, including macular degeneration,1 detachment (RD),2–4 diabetic retinopathy,5 retinopathy of prematurity,6 and retinitis pigmentosa.7 In these pathologic conditions, photoreceptors undergo apoptosis.2,5–7 Therefore, new insights about the mechanisms that underlie photoreceptor degeneration ocular diseases would be clinical interest could lead to neuroprotective treatments. Previously, we used rodent model RD clarify mechanism RD-induced degeneration. We found apoptosis went through a caspase-dependent8,9 or caspase-independent pathway.10 Furthermore, monocytes recruited upregulation monocyte chemoattractant protein (MCP)-1 Muller glial cells play neurodestructive role degeneration.11,12 Tumor necrosis factor (TNF)-α is synthesized, mainly monocytes, as 26-kDa precursor13 cleaved proteolytically secreted 17-kDa protein.14 TNFα acts via either low-affinity TNF receptor (TNFR1) high-affinity (TNFR2).15 upregulated neurodegenerative disorders multiple sclerosis, Parkinson's disease, Alzheimer's disease suppression has demonstrated therapeutic effects.16 ophthalmic vitreous samples from patients with contain significantly higher levels than other such hole idiopathic premacular fibrosis.17,18 However, elevated on remains unclear. Recently, TNFα-suppressing monoclonal antibodies infliximab have been successfully treat inflammatory Behcet's disease,19 diffuse subretinal fibrosis (DSF) syndrome,20 posterior scleritis,21 vascular tumors,22 neovascular age-related degeneration.23 Thus, if plays degeneration, anti-TNFα treatment may good candidate for diseases. this study, induced mice deficient TNF, TNFR1, TNFR2 investigated pathway apoptosis.