The oil spill in ageing Bruch membrane

Curcio, Christine A.; Johnson, Mark; Rudolf, Martin; Huang, Joe

doi:10.1136/bjophthalmol-2011-300344

Cited by 314 publications

(340 citation statements)

References 94 publications

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“…There is compelling evidence for the production and secretion of cholesterol-containing lipids and lipoprotein particles, secreted at least partly by the RPE (7,8), that are recruited and retained in the aging Bruch's membrane (9)(10)(11)(12)(13)(14). However, there is no unifying explanation of how and why proteins are recruited and retained at the RPE/choriocapillaris interface.…”

mentioning

confidence: 99%

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye

Thompson

Reffatto

Bundy³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

108

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Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5–20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch’s membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch’s membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.

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mentioning

confidence: 99%

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye

Thompson

Reffatto

Bundy³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

101

108

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“…The "lipid wall" has been proposed as a necessary, but not sufficient, step in drusen biogenesis (Curcio et al, 2011). Oxidation of the trapped lipoproteins results in the M A N U S C R I P T…”

Section: Overview Of Drusen Biogenesismentioning

confidence: 99%

Differentiating drusen: Drusen and drusen-like appearances associated with ageing, age-related macular degeneration, inherited eye disease and other pathological processes

Khan

Mahroo

Khan

et al. 2016

Progress in Retinal and Eye Research

166

154

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Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research.

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“…79 In particular, the lipid component is considered by some to represent a significant factor in the pathology of AMD. 80 Different types of drusen contain different materials. 81 Formation of drusen has been attributed to RPE cell waste deposits and/or to accumulating material derived from the choroid in reverse flow.…”

Section: Pathology Of Macular Degenerationmentioning

confidence: 99%