Immunohistochemical light and electron microscopy of basal laminar deposit

Schaft, Theo L. van der; Mooy, Cornelia M.; Bruijn, W. C. de; Bosman, Fred T.; Jong, P.T.V.M. de

doi:10.1007/bf00176436

Cited by 77 publications

(47 citation statements)

References 18 publications

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“…The location and composition of these deposits distinguish aging from AMD. Basal laminar deposits (BlamD), which form between the RPE cell and basement membrane, are a normal aging change early, but become specific for AMD when they become thick and contain cellular debris, 'long spaced collagen', membranous structures, lipid, and inflammatory proteins (Sarks, 1976;Newsome et al, 1987;Green and Enger, 1993;van der Schaft et al, 1994;Spraul et al, 1996;Spraul and Grossniklaus, 1997;Curcio and Millican, 1999;Anderson and Ozaki, 2001;Johnson et al, 2002;Leu et al, 2002). The most sensitive and specific histopathologic marker of AMD is basal linear deposits (BlinD), which form in the inner collagenous layer of Bruch's membrane.…”

Section: Discussionmentioning

confidence: 99%

“…The composition and location of these deposits distinguishes chronological aging from age-related disease. Basal laminar deposits, which develop between the RPE cell and basement membrane, are specific for age-related macular degeneration (AMD) when they are thick and contain heterogeneous debris such as long spaced collagen (Sarks, 1976;Newsome et al, 1987;Green and Enger, 1993;van der Schaft et al, 1994;Spraul et al, 1996;Spraul and Grossniklaus, 1997;Curcio and Millican, 1999;Anderson et al, 2001;Johnson et al, 2002;Leu et al, 2002). Basal linear deposits occur within the inner collagenous layer, and are the most specific basal deposit for AMD (Sarks, 1976;Newsome et al, 1987;Green and Enger, 1993;van der Schaft et al, 1994;Spraul et al, 1996;Spraul and Grossniklaus, 1997;Curcio and Millican, 1999;Anderson et al, 2001;Johnson et al, 2002;Leu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas

Yamada

Ishibashi

et al. 2006

Experimental Eye Research

100

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Basal deposits within Bruch's membrane are associated with aging and age-related macular degeneration (AMD) although the factors causing their formation are incompletely understood. Advanced glycation endproducts (AGEs) accumulate in Bruch's membrane including basal deposits and drusen with aging. One mechanism by which AGEs alter a cell's phenotype is via AGE receptors. The purpose of this study was to immunolocalize and quantify the expression of AGE receptors by RPE cells associated with basal deposits or normal Bruch's membrane that were microdissected from human maculas. Postmortem eyes from 14 aged control donors and five donors with non-neovascular AMD were cryopreserved. RPE cells associated with normal Bruch's membrane or basal deposits were laser capture microdissected. The RNA was extracted and used for RT-qPCR to quantify the expression of RAGE, AGE R1, AGE R2, and AGE R3. Streptavidin alkaline phosphatase immunohistochemistry for these receptors was also performed and sections were bleached from 14 normal and nine AMD donors. RT-qPCR showed significant upregulation of RAGE, AGE R1, and AGE R3 in RPE cells overlying basal deposits compared to cells attached to morphologically normal Bruch's membrane. Immunohistochemical analysis for RAGE, AGER1, R2, and R3 showed diffuse, light staining of RPE cells and strong choriocapillaris staining in areas of normal Bruch's membrane. In areas of basal deposits, the RPE had more intense staining for RAGE and AGER1 compared to regions of normal Bruch's membrane. These results suggest that AGE receptors could influence the formation of basal deposits during aging and AMD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas

Yamada

Ishibashi

et al. 2006

Experimental Eye Research

100

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“…Early deposit formation is the result of normal basement membrane component expansion (38)(39)(40). Further evidence of overlap between D-gal-induced transcriptional changes in the RPEchoroid and atherosclerosis is the altered expression of matrix genes.…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: A comprehensive transcriptional response

Tian

Ishibashi

et al. 2005

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

119

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Advanced glycation endproduct (AGE) formation is a trigger for the onset of age-related disease. To evaluate AGE-induced change in the ocular fundus, 5-mo-old C57BL͞6 mice were given low-dose D-galactose (D-gal) for 8 wk and evaluated by AGE fluorescence, electroretinography (ERG), electron microscopy, and microarray analysis for 20 wk. Although AGE fluorescence was increased in D-gal-treated retinal pigment epithelium (RPE)-choroid compared with controls at all time points, ERG showed no AGE-induced functional toxicity. Progressive ultrastructural aging in the RPEchoroid was associated temporally with a transcriptional response of early inflammation, matrix expansion, and aberrant lipid processing and, later, down-regulation of energy metabolism genes, up-regulation of crystallin genes, and altered expression of cell structure genes. The overall transcriptome is similar to the generalized aging response of unrelated cell types. A subset of transcriptional changes is similar to early atherosclerosis, a chronic inflammatory disease characterized by matrix expansion and lipid deposition. These changes suggest an important contribution of a single environmental stimulus to the complex aging response.transcriptome ͉ basal deposit ͉ Bruch's membrane A ging is a multifactorial process associated with physiological decline. Prior efforts to comprehensively identify and evaluate contributory factors have benefited from global assessment strategies such as microarray analysis. Although some general trends in the transcriptional responses to aging have been identified in diverse tissues such as skeletal muscle, cardiac muscle, and brain, the aging kidney is without modification (1-4).Normal vision requires a functional retinal pigment epithelium (RPE)-Bruch's membrane (BM)-choroid to sustain the neurosensory retina. Photooxidative stress, photoreceptor outer segment shedding, lipid peroxidation, high metabolic requirements, and increased oxygen demand result in high levels of oxidative stress to the fundus. As a result, with aging, the RPE and choriocapillaris endothelium dedifferentiate (5, 6). The most significant changes are basal deposits that develop within BM, a pentalaminar matrix that includes the RPE and choriocapillaris endothelial basement membrane (5, 6). The location and composition of the deposits correlates with the development of age-related disease (5, 6). The molecular events surrounding basal deposit formation, however, are poorly characterized.Advanced glycation endproducts (AGEs) are a heterogeneous group of reaction products that form between a protein's primary amino group and a carbohydrate-derived aldehyde group. A substantial amount of literature indicates that AGEs exacerbate and accelerate aging change and contribute to the early phases of age-related disease, including atherosclerosis, cataract, neurodegenerative disease, renal failure, arthritis, and age-related macular degeneration (AMD) (7,8). We found that AGEs accumulate with age in human BM and immunolocalize to basal deposits (9-11). We...

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“…These include Sorsby's fundus dystrophy, late onset retinal degeneration (LORD), adult foveomacular pigment epithelial dystrophy and Malattia leventinese (115). The molecular composition and origin of BLamD have not yet been identified (116)(117)(118), but their morphological similarity to long-spacing collagen is striking. Electron microscopy has revealed that their banding pattern matches that of type VI collagen (119).…”

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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Immunohistochemical light and electron microscopy of basal laminar deposit

Cited by 77 publications

References 18 publications

The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas

The expression of advanced glycation endproduct receptors in rpe cells associated with basal deposits in human maculas

Advanced glycation endproduct-induced aging of the retinal pigment epithelium and choroid: A comprehensive transcriptional response

Age‐related macular degeneration—emerging pathogenetic and therapeutic concepts

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