title: Complement system activation and endothelial dysfunction in patients with age-related macular degeneration (AMD): possible relationship between AMD and atherosclerosis.
abstract: Age-related macular degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). First, an association between AS and AMD is apparent from the analyses of the histological and biochemical structure of atherosclerotic plaques in the vascular walls and retinal drusen, the hallmark of AMD. Second, there is considerable evidence implicating endothelial dysfunction in the pathogenesis of both disorders, and cellular oxidative stress appears to be a common denominator underlying this process. Moreover, there are observations that the complement system (CS) triggering inflammatory response contributes to the onset and advancement of both diseases. The CS plays a role in the generation of drusen and neovascularization in AMD as well as in vascular endothelium activation, cell damage and ultimately atherosclerotic plaque formation in the course of systemic arteriosclerosis. It is widely recognized that both AMD and AS are not only related to local stimulation of the CS, but also result in its systemic activation. In addition, a specific Y402H polymorphism of the complement inhibitor factor H has been found to be associated with the incidence of both AMD and AS. Here, we propose a linking hypothesis between CS activation, endothelial dysfunction and the pathogenesis of two common and age-related pathological processes, AS and AMD. We also discuss the potential therapeutic value of pharmacological modulation of CS activation in these disorders.
authors: Department of Ophthalmology, Pomeranian Medical University, Szczecin, Poland.
authors: Anna
authors: A
authors: Machalińska
authors: Miłosz P
authors: MP
authors: Kawa
authors: Wojciech
authors: W
authors: Marlicz
authors: Bogusław
authors: B
authors: Machaliński
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000503:physiopathology*; D003167:Complement Activation / Q000502:physiology*; D017242:Complement Factor H / Q000235:genetics; D003165:Complement System Proteins / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide
chemical_list: D017242:Complement Factor H; D003165:Complement System Proteins