Bruch's membrane age-related changes vary by region

Newsome, David A.; Huh, Warne; Green, W R

doi:10.3109/02713688709025231

Cited by 91 publications

(55 citation statements)

References 18 publications

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“…In our study, long spacing collagen was observed only when examining the tissues using OTAP thin-sectioning TEM (data not shown). In OTAP images, the long spacing collagens found in BrM demonstrated morphological features similar to those previously described in other studies (Grindle and Marshall, 1978;Newsome et al, 1987).…”

Section: Inclusions Seen In Brm Using Qfdesupporting

confidence: 73%

“…The long spacing collagen, described in other morphological studies of BrM (Hogan and Alvarado, 1967;Grindle and Marshall, 1978;Killingsworth, 1987;Newsome et al, 1987), was not identified in our QFDE preparations. In our study, long spacing collagen was observed only when examining the tissues using OTAP thin-sectioning TEM (data not shown).…”

Section: Inclusions Seen In Brm Using Qfdementioning

confidence: 61%

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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 Seen In Brm Using Qfdesupporting

confidence: 73%

Section: Inclusions Seen In Brm Using Qfdementioning

confidence: 61%

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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“…23,31,32 Moreover, there is evidence that BM fragmentation can trigger proinflammatory responses that might accelerate AMD process. [33][34][35] In addition to BM modifications, drusen deposits, a hallmark of AMD, accumulate between the RPE and BM. Drusens are rich in ECM proteins such as vitronectin (VN) and many inflammatory markers.…”

Section: Introductionmentioning

confidence: 99%

“…Drusens are rich in ECM proteins such as vitronectin (VN) and many inflammatory markers. 23,33,36,37 Thus, one of the important tasks of transplanted hESC-RPE is to produce sufficient ECM to restore the functions of the damaged BM if no BM mimicking nonbiodegradable biomaterial is used with cells. 16,17 Previously, it has been shown that ECM affects the early stage differentiation of hPSCs into neural progenitors and neurons, 38 retinal progenitor cells, 39,40 and RPE cells.…”

Section: Introductionmentioning

confidence: 99%

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Sorkio

Hongisto

Kaarniranta

et al. 2014

Tissue Engineering Part A

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Extracellular matrix (ECM) interactions play a vital role in cell morphology, migration, proliferation, and differentiation of cells. We investigated the role of ECM proteins on the structure and function of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells during their differentiation and maturation from hESCs into RPE cells in adherent differentiation cultures on several human ECM proteins found in native human Bruch's membrane, namely, collagen I, collagen IV, laminin, fibronectin, and vitronectin, as well as on commercial substrates of xeno-free CELLstartÔ and MatrigelÔ. Cell pigmentation, expression of RPE-specific proteins, fine structure, as well as the production of basal lamina by hESC-RPE on different protein coatings were evaluated after 140 days of differentiation. The integrity of hESC-RPE epithelium and barrier properties on different coatings were investigated by measuring transepithelial resistance. All coatings supported the differentiation of hESC-RPE cells as demonstrated by early onset of cell pigmentation and further maturation to RPE monolayers after enrichment. Mature RPE phenotype was verified by RPE-specific gene and protein expression, correct epithelial polarization, and phagocytic activity. Significant differences were found in the degree of RPE cell pigmentation and tightness of epithelial barrier between different coatings. Further, the thickness of self-assembled basal lamina and secretion of the key ECM proteins found in the basement membrane of the native RPE varied between hESC-RPE cultured on compared protein coatings. In conclusion, this study shows that the cell culture substrate has a major effect on the structure and basal lamina production during the differentiation and maturation of hESC-RPE potentially influencing the success of cell integrations and survival after cell transplantation.

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“…Classically, these BM defects have been described as fragmentation or fracturing in association with calcification (81)(82)(83)(84)(85). Additional age-related changes in BM are typified by: 1) progressive thickening of the two collagenous layers; 2) modification and degeneration of collagen and elastin; 3) increased levels of advanced glycation end products, noncollagenous proteins and lipids; and 4) accumulation of several types of sub-RPE deposits (86)(87)(88)(89)(90)(91)(92)(93)(94)(95). It has also been suggested that the age-related abnormalities in BM eventually lead to photoreceptor degeneration as a result of increased hydrophobicity, reduced permeability, and impaired nutrient exchange between the choroid and the RPE.…”

Section: Morphological Correlates Of Early Amdmentioning

confidence: 99%

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

et al. 2006

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Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden.Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage 'wet' form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common 'dry' AMD, except for the use of antioxidants that delay progression in 20%-25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene-which encodes the major inhibitor of the complement alternative pathway-is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development of novel diagnostic and therapeutic approaches for this disease that will dramatically improve the quality of our prolonged lifespan.

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Bruch's membrane age-related changes vary by region

Cited by 91 publications

References 18 publications

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

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

Structure and Barrier Properties of Human Embryonic Stem Cell–Derived Retinal Pigment Epithelial Cells Are Affected by Extracellular Matrix Protein Coating

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

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