Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers.
نویسندگان
چکیده
Protein misfolding and aggregation are thought to underlie the pathogenesis of many amyloid diseases, such as Alzheimer and Parkinson diseases, whereby a stepwise protein misfolding process begins with the conversion of soluble protein monomers to prefibrillar oligomers and progresses to the formation of insoluble amyloid fibrils. Drusen are extracellular deposits found in aging eyes and in eyes afflicted with age-related macular degeneration (AMD). Recent characterizations of drusen have revealed protein components that are shared with amyloid deposits. However, characteristic amyloid fibrils have thus far not been identified in drusen. In this study, we tested the hypothesis that nonfibrillar oligomers may be a common link in amyloid diseases. Oligomers consisting of distinct amyloidogenic proteins and peptides can be detected by a recently developed antibody that is thought to recognize a common structure. Notably, oligomers exhibit cellular toxicity, which suggests that they play a role in the pathogenesis of neurodegenerative diseases. Through use of the anti-oligomer antibody, we came to observe the presence of nonfibrillar, toxic oligomers in drusen. Conversely, no reactivity was observed in age-matched control eyes without drusen. These results suggest that amyloid oligomers may be involved in drusen biogenesis and that similar protein misfolding processes may occur in AMD and amyloid diseases.
منابع مشابه
Association of Nonfibrillar Amyloid Oligomers with Drusen of Aging and Age-related Macular Degeneration
متن کامل
Drusen and Sub Retinal Drusenoid Deposits ( SDD ) in Age Related Macular Degeneration
Purpose: To review drusen and sub retinal drusenoid deposits in age related macular degeneration as regards their pathogenesis, morphology, differentiation and their importance as regards the visual prognosis of age related macular degeneration (AMD). Results: Each type of drusen or drusenoid deposits has a different visual prognosis, and the differentiation of them using multimodal imaging tes...
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PURPOSE Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the elderly. Increased understanding of the pathogenesis is necessary. Amyloid-beta (Abeta), a major extracellular deposit in Alzheimer's disease plaques, has recently been found in drusen, the hallmark extracellular deposit in AMD. The goal of this study was to characterize the distribution a...
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ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 116 2 شماره
صفحات -
تاریخ انتشار 2006