Age-related Macular Degeneration Histopathologic Studies

Green, W Richard; Enger, Cheryl

doi:10.1097/00006982-200507001-00015

Cited by 153 publications

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“…Basal deposits are the strongest histopathological marker of aging and age-related disease (Sarks, 1976;Green and Enger, 1993;Spraul et al, 1996;Spraul and Grossniklaus, 1997;Curcio and Millican, 1999). The location and composition of these deposits distinguish aging from AMD.…”

Section: Discussionmentioning

confidence: 99%

“…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

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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: Discussionmentioning

confidence: 99%

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

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“…Photoreceptor loss has been described, for instance in patients with neovascular AMD. 22 When photoreceptor cell bodies are damaged or die, their axons are likewise affected, leading to disruption of the radially symmetric birefringence of the Henle fibre layer and subsequently to disruption of the typical bowtie pattern. 15,20 The presence of the bowtie pattern was evaluated in eyes with subfoveal choroidal neovascularization by Katsanos et al to investigate whether choroidal neovascularization (CNV) would influence the measured retardation in SLP.…”

Section: Introductionmentioning

confidence: 99%

Relationship between foveal birefringence and visual acuity in neovascular age-related macular degeneration

Weber

Elsner

Miura

et al. 2006

Eye

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Purpose To investigate the relationship between visual acuity and foveal birefringence in patients with neovascular age-related macular degeneration. Methods In total, 40 patients with choroidal neovascularization underwent macular imaging with scanning laser polarimetry. Bowtie patterns, typically seen in birefringence images of the macula, were evaluated and classified into three categories: (1) regular bowtie present; (2) bowtie present, but disrupted; and (3) no bowtie present. The relation of the bowtie appearance to the best-corrected logMAR visual acuities was tested (ANOVA). Results Mean visual acuity was best for the group that had regular bowties (mean logMAR ¼ 0.34) and differed statistically significantly from the disrupted bowtie group and no bowtie group (P ¼ 0.01 and 0.0007). Ages for the three groups did not differ (P ¼ 0.31). Conclusions Appearance of a regular bowtie indicates a substantially intact Henle fibre layer with the potential for good visual function, despite the presence of underlying pathology. Conversely, disruption or absence of a bowtie may indicate severe damage to the photoreceptors, consistent with the finding of poorer visual acuity.

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“…Deposits in Bruch's membrane include drusen and basal deposits (flat and diffuse deposits beneath the RPE that include both basal laminar and basal linear deposits, distinguished ultrastructurally) (Green and Enger, 1993).…”

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confidence: 99%

Fibulin-5 distribution in human eyes: Relevance to age-related macular degeneration

Mullins¹,

Olvera²,

Clark³

et al. 2007

Experimental Eye Research

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Fibulin-5 is an extracellular matrix glycoprotein that participates in elastogenesis. Mutations in the gene for fibulin-5 have been found to be associated with age-related macular degeneration. Little is known, however, about the expression of this gene in normal eyes or eyes with age-related macular degeneration. In this study we evaluated the expression of the fibulin-5 protein in human donor eyes and localized this protein to Bruch's membrane and the intercapillary pillars of the choriocapillaris in normal eyes. In eyes with age-related macular degeneration, fibulin-5 was localized to pathologic basal deposits beneath the retinal pigment epithelium as well as some small drusen. These results suggest that fibulin-5 may promote extracellular deposit formation in macular degeneration. Keywordsage-related macular degeneration; fibulins; extracellular matrix; Bruch's membrane Bruch's membrane is a complex structure composed of 5 layers of extracellular matrix located between the retinal pigment epithelium (RPE) and the choriocapillaris. Bruch's membrane plays a number of important roles in normal retinal physiology. Oxygen, glucose and growth factors derived from the choroidal vasculature must pass through this tissue to supply the photoreceptor cells and RPE, while wastes derived from these highly metabolically active cells must pass in the opposite direction to be removed by the choroidal vasculature. In addition, Bruch's membrane is a site for RPE adhesion and also serves as a barrier to neovascularization, as ruptures in this structure are associated with abnormal angiogenesis from the choroid into the retina.During normal aging, and especially in age-related macular degeneration (AMD), Bruch's membrane undergoes morphological changes with extracellular deposit formation. Deposits in Bruch's membrane include drusen and basal deposits (flat and diffuse deposits beneath the Send correspondence to:

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Age-related Macular Degeneration Histopathologic Studies

Cited by 153 publications

References 0 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

Relationship between foveal birefringence and visual acuity in neovascular age-related macular degeneration

Fibulin-5 distribution in human eyes: Relevance to age-related macular degeneration

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