Histologic Features of the Early Stages of Age-related Macular Degeneration

Schaft, Theo L. van der; Mooy, Cornelia M.; Bruijn, W. C. de; Oron, Frans G.; Mulder, Paul; Jong, P.T.V.M. de

doi:10.1016/s0161-6420(92)31982-7

Cited by 152 publications

(70 citation statements)

References 17 publications

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“…In another study, Pauleikhoff et al (1990) indicated the appearance of small membrane-bound vesicles and membrane fragments. Other studies also reported membranous debris (Curcio and Millican 1999;Curcio et al, 2005a), long spacing collagens (Sarks, 1976;van der Schaft et al, 1991), drusen (Green and Enger, 1993;Sarks et al, 1999;Hageman and Mullins, 1999)), and fine granules in BrM (Killingsworth, 1987;Curcio and Millican 1999). In our studies, we found three types of inclusions in QFDE images: LLPs, SGs, and membrane-like structures.…”

Section: Inclusions Found In Brmsupporting

confidence: 79%

“…These inclusions include advanced glycation endproducts (AGEs), coated vesiclelike bodies, spiked coated vesicle-like bodies, electron-lucent droplets, membranous debris, coated membrane-bound bodies (CMBBs), long spacing collagen and lipoprotein-like particles (LLPs) (Hogan and Alvarado, 1967;Grindle and Marshall, 1978;Feeney-Burns and Ellersieck, 1985;Killingsworth, 1987;van der Schaft et al, 1991;Handa et al, 1999;Ruberti et al, 2003;Yamada et al, 2006). In the later stage of human life, these inclusions presumably fuse or aggregate to form drusen and the basal deposits that are associated with age-related macular degeneration (Sarks, 1976;Pauleikhoff et al, 1990;van der Schaft et al, 1992;Green and Enger, 1993;Curcio and Millican, 1999). The accumulation of these inclusions may impede physiologic transport through this region (Hogan and Alvarado, 1967;Killingsworth, 1987;Curcio and Millican, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch

Huang

Presley

Chimento

et al. 2007

Experimental Eye Research

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Lipid-containing inclusions have been observed in human Bruch's membrane (BrM) and are postulated to be associated with age-related maculopathy (ARM), a major cause of legal blindness in developed countries. The dehydration associated with specimen preparation for thin-section transmission electron microscopy causes loss of these inclusions. Better preservation of the ultrastructure of the inclusions and tissue is achieved by using a quick-freeze/deep-etch preparation. We use this technique to examine normal human macular BrM in order to characterize the deposition of the lipid-rich inclusions and their age-related accumulation within different layers of the tissue. We find that various inclusions mentioned in other studies can be formed by combinations of three basic structures: lipoprotein-like particles (LLPs), small granules (SGs) and membrane-like structures. These inclusions are associated with collagen and elastic fibrils by fine filaments. In younger eyes, these inclusions are found mostly in the elastic (EL) and outer collageneous layer (OCL) and occupy a small fraction of the interfibrillar spacing. As age increases, LLPs and SGs gradually fill the interfibrillar spacing of the EL and inner collageneous layer (ICL) of the tissue, and later form a new sublayer, the lipid wall, within the boundary region between the basal lamina of retinal pigment epithelium (RPE) and ICL. Because the formation of the lipid wall only occurs after these inclusions fill the ICL, and it seems unlikely that the LLPs can pass through the packed layer, this result suggests a possible RPE origin of the LLPs that make up the lipid wall.

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Section: Inclusions Found In Brmsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch

Huang

Presley

Chimento

et al. 2007

Experimental Eye Research

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“…BLD was arbitrarily graded as thin or thick according to whether it was or was not taller than half the height of a normal RPE cell. 15 The late component was always present when BLD became thick. Basal linear deposit, on the other hand, was seen only on electron microscopy as a layer of membranous debris external to the RPE basement membrane and is not described in this report.…”

Section: Methodsmentioning

confidence: 99%

Adult vitelliform macular degeneration: a clinicopathological study

Arnold

Sarks

Killingsworth

et al. 2003

Eye

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Aims/background The yellow lesions of adult vitelliform macular degeneration (AVMD) slowly fade, progressing to hyperpigmentation or atrophy. This study aims to provide further observations on the location and nature of the vitelliform material. Methods This report describes the clinicopathological correlation of four eyes with AVMD. A retrospective histopathological study of a further 526 aged eyes previously graded for the stage of age-related macular degeneration (AMD) found another 10 eyes with similar pathology. Results The predominant finding was a collection of extracellular material beneath the sensory retina at the fovea. This material was derived internally from photoreceptor outer segments and externally from the retinal pigment epithelium (RPE), the latter first undergoing hypertrophy and then disruption and attenuation. Fallout of foveal cones occurred over these lesions and the inner retina was thinned, which may explain macular hole formation in this condition. All affected eyes showed histopathological evidence of AMD. Conclusions This study confirms that the vitelliform lesions of AVMD lie beneath the sensory retina. In contrast to previous reports, however, it is proposed that the lesions comprise mainly extracellular material consisting of photoreceptor debris, possibly the result of faulty phagocytosis by the RPE, mixed with pigment liberated as the RPE undergoes disruption. The vitelliform lesions therefore are a marker for the area of maximal RPE disturbance.

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“…Drusen are defi ned histologically as focal, domeshaped lesions between the RPE basal lamina and the inner collagenous layer of BrM. They are found, at least in small numbers, in most older adults ( 46,47 ). Molecular constituents of drusen, virtually all identifi ed during the last decade, include vitronectin, tissue inhibitor of metalloproteinase 3 (TIMP-3), complement factor H, fi brillar and nonfi brillar contents are much more highly enriched in UC than the membranes of surrounding cells ( 24,55,58 ).…”

Section: Histopathology Of Extracellular Lesionsmentioning

confidence: 99%