PURPOSE: The accumulation of numerous or confluent drusen, especially in the macula, is a significant risk factor for the development of @entity1020 ( @entity1020 ). Identifying the origin and molecular composition of these deposits, therefore, has been an important, yet elusive, objective for many decades. Recently, a more complete profile of the molecular composition of drusen has emerged. DESIGN: In this focused review, we discuss these new findings and their implications for the pathogenic events that give rise to drusen and @entity1020 . METHODS: Tissue specimens from one or both eyes of more than 400 @entity1 donors were examined by light, confocal or electron microscopy, in conjunction with antibodies to specific @entity10983 , to help characterize the transitional events in drusen biogenesis. Quantification of messenger RNA from the @entity989 ( @entity989 )/choroid of donor eyes was used to determine if local ocular sources for drusen-associated molecules exist. RESULTS: The results indicate that cellular remnants and debris derived from degenerate @entity989 cells become sequestered between the @entity989 basal lamina and Bruch's membrane. We propose that this cellular debris constitutes a chronic inflammatory stimulus, and a potential "nucleation" site for drusen formation. The entrapped cellular debris then becomes the target of encapsulation by a variety of inflammatory mediators, some of which are contributed by the @entity989 and, perhaps, other local cell types; and some of which are extravasated from the choroidal circulation. CONCLUSIONS: The results support a role for @entity32 in drusen biogenesis, and suggest that it is analogous to the process that occurs in other age-related diseases, such as @entity195 and @entity731 , where accumulation of extracellular plaques and deposits elicits a local chronic inflammatory response that exacerbates the effects of primary pathogenic stimuli.

A role for XXXX in the formation of drusen in the aging eye.

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['local inflammation'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity10983 :: ('MESH:D015593', 'Disease') :: ['drusen-associated proteins'] @entity195 :: ('MESH:D000544', 'Disease') :: ["Alzheimer's disease"] @entity989 :: ('MESH:D012164', 'Disease') :: ['retinal pigment epithelium', 'RPE'] @entity1020 :: ('MESH:D008268', 'Disease') :: ['AMD', 'age-related macular degeneration']
@entity32 :: (MESH:D007249,Disease) :: ['local inflammation']
