AMD and Atherosclerosis coincidence: the role of complement system activation and endothelial dysfunction

Abstract

AbstractPurpose Age‐related Macular Degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). There is considerable evidence implicating endothelial dysfunction in the pathogenesis of both disorders, and complement system (CS) activation appears to be a common denominator underlying those processes. It is widely recognised that both AMD and AS are not only related to local stimulation of the CS, but also result in its systemic activation.Methods We recruited 77 subjects with clinical diagnosis of AMD and 46 age/sex–matched controls. The concentration of C3a‐desArg complement compound,the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) was measured in the subjects’ peripheral blood (PB).Results We demonstrated increased numbers of CECs in the PB of AMD patients, a finding which reflects a severe vascular disturbance and clearly indicates that there is an endothelial alteration accompanying AMD. We also postulated that EPC enumeration could serve as a novel method for the assessment of AMD‐related choroidal neovascularisation and demonstrated significantly elevated EPC counts in the PB of patients with the exudative form of AMD.We found that the levels of C3a‐desArg were significantly elevated in plasma of exudative AMD patients compared to the control group. Additionally, the patients and controls with documented AS displayed significantly higher levels of C3a‐desArg in PB compared to subjects without AS.Conclusion We propose a linking hypothesis between CS activation, endothelial dysfunction and the pathogenesis of two common and age‐related pathological processes, AS and AMD.(Grant‐N N402 172137)