Monocyte activation in patients with age-related macular degeneration: a biomarker of risk for choroidal neovascularization?

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 alpha (TNF-alpha) and by correlating its expression with dry and wet AMD. 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-alpha release from cultured macrophages in response to retinal pigment epithelium-derived blebs and cytokines or TNF-alpha messenger RNA content by reverse transcriptase-polymerase chain reaction. In human monocytes obtained from controls and AMD patients, TNF-alpha 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-alpha expression was observed among different patients. Patients with monocytes that expressed the greatest amount of TNF-alpha demonstrated higher prevalence of choroidal neovascularization. Both controls and AMD patients vary in the activation state (defined as TNF-alpha expression) of circulating monocytes. Partially active monocytes, defined as high TNF-alpha expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization. Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.