Fig. 3.

Schema of the role of lipids in drusen and subretinal drusenoid deposit formation. a In the cone-rich fovea, the high cholesterol content of cones, along with lipids derived from the circulation due to a high cholesterol diet, induces apoB100 lipoprotein formation that is basally secreted. Due to age-related Bruch’s membrane changes, lipoproteins accumulate, forming the lipid wall. In the rod-rich parafovea, reverse cholesterol transport mediated through ABCA1 releases cholesterol to apoE and apoA1, forming high-density lipoproteins for the recycling of lipids including docohexanoic acid and cholesterol to rods. b Hydroxyapatite forms around retained lipids and lipoproteins, and combined with lipoprotein oxidation, induces an inflammatory response with the accumulation of inflammatory debris, leading to basal deposit and drusen formation. In the subretinal space, dysfunction of reverse cholesterol transport can lead to lipid accumulation, which induces an inflammatory response, forming subretinal drusenoid deposits. AGEs advanced glycation endproducts, BD basal deposit, BrM Bruch’s membrane, CC choriocapillaris, CEP carboxyethyllysine, Chol cholesterol, ER endoplasmic reticulum, HAP hydroxyapatite, HDL high-density lipoprotein, HFC high-fat cholesterol diet, HSPG heparan sulfate proteoglycan, Lp apoB100 containing lipoprotein, Ly lysosome, Mono/macro monocyte/macrophage, RCT reverse cholesterol transport, ROS reactive oxygen species, SDD subretinal drusenoid deposit; yellow circle surrounded by red, apoB100 containing lipoprotein with surrounding HAP