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A Biomarker of Risk for Choroidal Neovascularization?

Scott W. Cousins, MD; Diego G. Espinosa-Heidmann, MD; Karl G. Csaky, MD, PhD

Arch Ophthalmol. 2004;122:1013-1018.

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 (TNF-) 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- release from cultured macrophages in response to retinal pigment epithelium–derived blebs and cytokines or TNF- messenger RNA content by reverse transcriptase–polymerase chain reaction.

Results  In human monocytes obtained from controls and AMD patients, TNF- 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- expression was observed among different patients. Patients with monocytes that expressed the greatest amount of TNF- demonstrated higher prevalence of choroidal neovascularization.

Conclusions  Both controls and AMD patients vary in the activation state (defined as TNF- expression) of circulating monocytes. Partially active monocytes, defined as high TNF- expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization.

Clinical Relevance  Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.

From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Fla (Drs Cousins and Espinosa-Heidmann); and the National Eye Institute, National Institutes of Health, Bethesda, Md (Dr Csaky).

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