Objective: To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of the proinflammatory and angiogenic factor tumor necrosis factor α (TNF-α) and by correlating its expression with dry and wet AMD. Methods: Circulating monocytes were obtained from the blood of patients with AMD or age-matched control subjects by gradient centrifugation. The monocytes were then analyzed for either TNF-α release from cultured macrophages in response to retinal pigment epithelium-derived blebs and cytokines or TNF-α messenger RNA content by reverse transcriptase-polymerase chain reaction. Results: In human monocytes obtained from controls and AMD patients, TNF-α was expressed by freshly isolated monocytes and produced by macrophages in culture after stimulation with retinal pigment epithelium-derived blebs. However, wide variability in TNF-α expression was observed among different patients. Patients with monocytes that expressed the greatest amount of TNF-α demonstrated higher prevalence of choroidal neovascularization. Conclusions: Both controls and AMD patients vary in the activation state (defined as TNF-α expression) of circulating monocytes. Partially active monocytes, defined as high TNF-α expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization. Clinical of Relevance: Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.
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