A role for local inflammation in the formation of druen in the aging eye

PURPOE: The accumulation of numerou or confluent druen, epecially in the macula, i a ignificant rik factor for the development of age-related macular degeneration (AMD). Identifying the origin and molecular compoition of thee depoit, therefore, ha been an important, yet eluive, objective for many decade. Recently, a more complete profile of the molecular compoition of druen ha emerged. DEIGN: In thi focued review, we dicu thee new finding and their implication for the pathogenic event that give rie to druen and AMD. METHOD: Tiue pecimen from one or both eye of more than 400 human donor were examined by light, confocal or electron microcopy, in conjunction with antibodie to pecific druen-aociated protein, to help characterize the tranitional event in druen biogenei. Quantification of meenger RNA from the retinal pigment epithelium (RPE)/choroid of donor eye wa ued to determine if local ocular ource for druen-aociated molecule exit. REULT: The reult indicate that cellular remnant and debri derived from degenerate RPE cell become equetered between the RPE baal lamina and Bruch’ membrane. We propoe that thi cellular debri contitute a chronic inflammatory timulu, and a potential “nucleation” ite for druen formation. The entrapped cellular debri then become the target of encapulation by a variety of inflammatory mediator, ome of which are contributed by the RPE and, perhap, other local cell type; and ome of which are extravaated from the choroidal circulation. CONCLUION: The reult upport a role for local inflammation in druen biogenei, and ugget that it i analogou to the proce that occur in other age-related dieae, uch a Alzheimer’ dieae and atherocleroi, where accumulation of extracellular plaque and depoit elicit a local chronic inflammatory repone that exacerbate the effect of primary pathogenic timuli.