Age-related Macular Degeneration

Age-related Macular Degeneration (AMD) is the leading cause of blindness in people over the age of 50. AMD is common, with an estimated 2 million people currently having the disease in the US and a projected 3 million by 2020. In AMD, there is progressive loss of retinal pigmented epithelium (RPE) cells and photoreceptor cells in the retinal macula. AMD is classified as "dry" (non-exudative) or "wet" (exudative). Early AMD is typically dry. Later on in the course of AMD, the wet form appears, characterized by neovascularization occurring under the RPE.

Although the exact cause of AMD is unknown, the complement system is central to its development. C5a, one of the most potent pro-inflammatory mediators of the complement system, contributes to the pathology of AMD through expression of adhesion molecules and mediating infiltration of monocytes/macrophages and polymorphonuclear cells such as neutrophils. It also stimulates RPE cells to secrete the pro-angiogenic vascular endothelial growth factor (VEGF), increases vascular permeability, induces basophil and mast cell degranulation and induces release of lysosomal proteases and oxidative free radicals, causing damage to RPE cells and photoreceptors. These events occurring in the macula lead to progressive vision loss.

Current treatment of AMD consists of photodynamic therapy (PT) and the VEGF inhibitors pegaptanib sodium and ranibizumab, which need to be injected intraocularly. PT showed evidence for halting but not improving the disease in some patients and the VEGF inhibitors are associated with complications including ocular membrane hemorrhage, vitreous floaters, and eye pain. Therefore, there remains a significant unmet medical need to treat patients with AMD.

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