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

Arch Ophthalmol. 2004 Jul;122(7):1013-8. doi: 10.1001/archopht.122.7.1013.


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 alpha (TNF-alpha) 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-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.

Results: 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.

Conclusions: 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.

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

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cells, Cultured
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism*
  • Female
  • Humans
  • Macrophage Activation / physiology
  • Macrophages / physiology
  • Macular Degeneration / complications
  • Macular Degeneration / metabolism*
  • Male
  • Middle Aged
  • Monocytes / physiology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*


  • Biomarkers
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha