Inflammation in AMD pathology

Age‐related macular degeneration (AMD) is a progressive retinal disease that leads to substantial irreversible vision loss in elderly patients. Two clinical categories of AMD are distinguished: the “dry” atrophic form and the exudative neovascular or “wet” form. There is neither a preventive therapy nor a cure for both forms, although recent efforts succeeded in a more effective treatment of the wet AMD with PDT and anti‐VEGF drugs. AMD is a multifactorial pathology which involves complex interaction of metabolic, genetic and environmental factors, with major biochemical‐clinical abnormalities seen in four functionally interrelated tissues: photoreceptors, retinal pigment epithelium, Bruch’s membrane and choriocapilaries. Four processes specifically contribute to the development of AMD pathology: lipofuscinogenesis (in RPE cells), drusogenesis (with drusen located between RPE and Bruch’s membrane), inflammation (local) and choroidal neovascularization (in wet form). Although the role of immune system and inflammation has been implicated in AMD pathogenesis for many years, an impetus to intensify the research in this direction gave a recent discovery of polymorphisms in genes that encode for elements of the complement system, including factor H (CFH; Y402H), factor B, and complement component 2. An increased activity of the complement alternative pathway due to the lack of or insufficient control by CFH appears to contribute to AMD progression via immunologic mechanism which drives inflammatory response. An arising question is whether blockade of overactive complement system will be a therapeutic strategy safe for patients and effective to prevent or slowing down the macula‐devastating and vision‐threatening disease. Supported by grant no. 503‐1023‐1 from Medical University of Lodz.