Element Analysis of the Early Stages of Age-Related Macular Degeneration

Schaft, Theo L. van der; Bruijn, W. C. de; Mooy, Cornelia M.; Ketelaars, Diane A. M.; Jong, P.T.V.M. de

doi:10.1001/archopht.1992.01080150087034

Cited by 39 publications

(15 citation statements)

References 20 publications

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“…However, compared with other calcium phosphates, HAP is much less soluble; more stable; mechanically harder; and, to our knowledge, solubilized physiologically only with acid treatment (21). Small internal spherules with calcium content have been noted in sub-RPE deposits before (20,22), but HAP has not been associated with these spherules.…”

Section: Significancementioning

confidence: 74%

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.

113

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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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Section: Significancementioning

confidence: 74%

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.

113

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“…Zinc concentration in ocular tissues has been determined by flame or flameless atomic absorption spectrophotometry [37,[43][44][45][46][47][48][49][50][51][52], neutron activation [53,54], X-ray fluorescence [16], electron probe microanalysis [55], inductively coupled plasma-mass spectrometry [56,57] and plasma emission spectrophotometry [58]. The amount of zinc varies greatly with age and the ocular tissue examined; however, the retina and uvea usually contain the highest concentrations (Table 1) [16,37,52,53,56,57,59 -62].…”

Section: Localization and Concentration Of Zinc In The Eyementioning

confidence: 99%

Zinc and the Eye

Grahn

Paterson

Gottschall‐Pass

et al. 2001

Journal of the American College of Nutrition

152

118

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Zinc, a trace element that influences cell metabolism through a variety of mechanisms, appears to play an integral role in maintaining normal ocular function. This element is present in high concentrations in ocular tissue, particularly in retina and choroid. Zinc deficiency has been shown in a number of species to result in a variety of gross, ultrastructural and electrophysiologic ocular manifestations. The physiological functions for zinc have been studied predominantly in retina and retinal pigment epithelium where zinc is believed to interact with taurine and vitamin A. modify photoreceptor plasma membranes, regulate the light-rhodopsin reaction, modulate synaptic transmission and serve as an antioxidant. Suboptimal zinc status in North America may influence the development and progression of several chronic eye diseases. Zinc supplementation trials and epidemiological studies have produced conflicting results concerning the role of zinc in age-related macular degeneration. Additional well-controlled supplementation trials are indicated to clarify the role of zinc in this disease. Future investigations must also expand our understanding of the mechanisms by which zinc regulates ocular morphology and function.

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“…7 Along with possible contributions from photic injury and oxidative stress, zinc deficiency is a suspected risk factor for AMD. 8−10 Low levels of macular zinc have been reported in AMD patients, 11 and oral zinc supplementation ameliorated the symptoms of AMD. 8,12,13 In cultured human RPE cells, zinc protected against oxidative damage.…”

Section: Introductionmentioning

confidence: 99%