Study supports complement-mediated hypothesis of AMD

This study published in September in the American Journal of Ophthalmology explores the implication of complement receptor 2 (CD21), complement receptor 1 (CD35) and the decay-accelerating factor (CD55) in the pathogenesis of age-related macular degeneration (AMD) by assessing their expression rates. The authors found that CD35 was expressed at a significantly higher frequency in patients with wet AMD compared with healthy controls. These findings support the complement-mediated hypothesis of AMD, reinforcing the conclusion that the complement system plays a key role in the process of AMD degeneration and demonstrating the involvement of the whole immune system through more regulative factors.

The authors assessed the differential expression of CD55, CD21 and CD35 in 50 unrelated AMD patients and 48 unrelated sex- and age-matched controls by analyzing blood samples using mean channel fluorescence with flow cytometry (fluorescence-activated cell sorting). They found that CD35 expression in AMD patients was significantly higher on monocytes (P = 0.00586), lymphocytes (P = 0.000605) and granulocytes (P < 0.000033). In contrast, there was no difference in expression of CD21 and CD55 between the cohorts.

The authors say that upregulation of complement receptors is driven by activated complement components, and the observed increase in CD35 expression reflects the activated state of the complement cascade in AMD patients. The results could provide evidence for greater activation of lymphocytes and neutrophilic granulocytes in these patients, which in turn assists in the destruction of antigens (e.g., microbes like Chlamydia pneumonia, which has already been correlated with AMD) by binding to them and making them easier targets for phagocytosis. The authors conclude that this overreaction of the whole immune system could lead to the destructive changes in the retinal pigment epithelium characteristic in AMD.