Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration

Sura, Amol; Chen, Ling; Messinger, Jeffrey D.; Swain, Thomas A.; McGwin, Gerald; Freund, K. Bailey; Curcio, Christine A.

doi:10.1167/iovs.61.13.19

Cited by 95 publications

(109 citation statements)

References 111 publications

(129 reference statements)

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“…Taken with our recent reports on BLamD and SDDs, 18 , 56 this report advances a comprehensive description of AMD pathology to support multimodal OCT-based clinical imaging and a multilayer progression timeline. Soft drusen are the earliest discovered and largest risk factor for progression to end stages.…”

Section: Discussionsupporting

confidence: 71%

“…Despite extraordinary epidemiologic evidence for causality, 2 drusen are just one of many actors in extant theories of AMD pathophysiology. One reason is that human eye studies require systematic tissue collection to capture all AMD stages and specialized techniques to differentiate soft drusen material from RPE-BL above and ICL below, 18 challenges we herein address.…”

Section: Discussionmentioning

confidence: 99%

“…As described, 18 Project MACULA ( https://projectmacula.org/ ) is an online digital microscope with high-resolution histology and annotated layer thicknesses of human donor eyes with and without AMD ( n = 139 total, 79 used herein). Our expectation was that accurate depiction and quantification of cell and tissue features in histology could leverage longitudinally tracked OCT in clinical trial image data sets and practices with long-standing OCT usage to generate a cellular-level timeline of disease.…”

Section: Methodsmentioning

confidence: 99%

“…The vertical dimension is expanded to highlight thin anatomic layers between outer segments and choriocapillaris and incorporated into the fourth outer retinal hyperreflective band of OCT. The trilaminar BrM 18 consists of inner collagenous (ICL), elastic (EL), and outer collagenous (OCL) layers. The RPE as an epithelium rests on a basal lamina (BL) of extracellular matrix (at left ).…”

mentioning

confidence: 99%

“… 107 The vertical bars show the third and fourth outer retinal hyperreflective bands of currently available spectral domain OCT, 15 with our interpretations. 18 The third band, called the interdigitation zone (IZ), corresponds to interleaved photoreceptor outer segments and RPE apical processes containing melanosomes. Fourth band components include RPE cell bodies and basal infoldings, RPE-BL, BLamD if present, contents of sub-RPE-BL space if present, and ICL-EL-OCL of BrM.…”

mentioning

confidence: 99%

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Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

Chen

Messinger

Kar

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Basal linear deposit (BLinD) is a thin layer of soft drusen material. To elucidate the biology of extracellular deposits conferring age-related macular degeneration (AMD) progression risk and inform multimodal clinical imaging based on optical coherence tomography (OCT), we examined lipid content and regional prevalence of BLinD, soft drusen, pre-BLinD, and subretinal drusenoid deposit (SDD) in AMD and non-AMD aged eyes. We estimated BLinD volume and illustrated its relation to type 1 macular neovascularization (MNV).METHODS. Donor eyes were classified as early to intermediate AMD (n = 25) and agematched controls (n = 54). In high-resolution histology, we assessed BLinD/soft drusen thickness at 836 and 1716 locations in AMD and control eyes, respectively. BLinD volume was estimated using solid geometry in donor eyes, one clinically characterized. RESULTS.BLinD, drusen, type 1 MNV, and fluid occupy the sub-RPE-basal laminar space. BLinD volume in a 3-mm diameter circle may be as much as 0.0315 mm 3 . Osmophilic lipid was more concentrated in BLinD/drusen than SDD. In the fovea, BLinD/drusen was prevalent in AMD eyes; pre-BLinD was prevalent in control eyes. SDD was low in the fovea and high in perifovea, especially in AMD eyes. CONCLUSIONS.Although invisible, BLinD may presage type 1 MNV. BLinD volume approaches the criterion OCT drusen volume of 0.03 mm 3 for AMD progression risk. BLinD culminates years of subfoveal lipid accumulation. SDD is detected relatively late in life, with currently unknown precursors. Deposit topography suggests one outer retinal lipid recycling system serving specialized cone and rod physiology, and its dysregulation in AMD is due to impaired transfer to the circulation.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

Chen

Messinger

Kar

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Ilex paraguariensis Extracts Prevent Oxidative Damage in a Mouse Model of Age‐Related Macular Degeneration

Tate

Marquioni-Ramella

Cerchiaro

et al. 2022

Molecular Nutrition Food Res

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Age-related macular degeneration (AMD), a chronic disease of the retina, leads to severe visual loss. AMD affects the retinal pigment epithelium (RPE) and the visual cells (photoreceptors). RPE failure, the first step of this disease, is associated with oxidative stress. Since antioxidants can slow down AMD progression, the intake of foods and drinks rich in antioxidant compounds may reduce retinal damage. Ilex paraguariensis (yerba mate, YM) extracts reduce oxidative damage of RPE cells in vitro as shown in previous study. Here, the effects of YM drinking on RPE and photoreceptor survival after oxidative damage with sodium iodate (NaIO3; SI) in a murine AMD model are described. Funduscopy and histology show that YM treatment prevents RPE and photoreceptor damage. YM also increases the expression of NRF2, the master antioxidant gene, and its effectors HO-1 and SOD2. In mice receiving YM and SI, the antioxidant response is larger than in mice receiving YM or SI alone. The YM drink also increases expression of RPE65, a gene that is involved in the functionality and survival of photoreceptors and RPE cells. The results suggest YM can play an important role in the prevention of retinal damage associated with oxidative stress, such as AMD.

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A High Fat “Western‐style” Diet Induces AMD‐Like Features in Wildtype Mice

Keeling

Lynn

Koh

et al. 2022

Molecular Nutrition Food Res

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Scope: The intake of a "Western-style" diet rich in fats is linked with developing retinopathies including age-related macular degeneration (AMD). Wildtype mice are given a high fat diet (HFD) to determine how unhealthy foods can bring about retinal degeneration. Methods and results: Following weaning, female C57BL/6 mice are maintained on standard chow (7% kcal fat, n = 29) or a HFD (45% kcal fat, n = 27) for 12 months. Animals were sacrificed following electroretinography (ERG) and their eyes analyzed by histology, confocal immunofluorescence, and transmission electron microscopy. HFD mice become obese, but showed normal retinal function compared to chow-fed controls. However, diminished 𝜷3tubulin labeling of retinal cross-sections indicated fewer/damaged neuronal processes in the inner plexiform layer. AMD-linked proteins clusterin and TIMP3 accumulated in the retinal pigment epithelium (RPE) and Bruch's membrane (BrM). Neutral lipids also deposited in the outer retinae of HFD mice. Ultrastructural analysis revealed disorganized photoreceptor outer segments, collapsed/misaligned RPE microvilli, vacuoles, convoluted basolateral RPE infolds and BrM changes. Basal laminar-like deposits were also present alongside abnormal choroidal endothelial cells. Conclusions: We show that prolonged exposure to an unhealthy "Western-style" diet alone can recapitulate early-intermediate AMD-like features in wildtype mice, highlighting the importance of diet and nutrition in the etiology of sight-loss.

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Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration

Cited by 95 publications

References 111 publications

Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

Biometrics, Impact, and Significance of Basal Linear Deposit and Subretinal Drusenoid Deposit in Age-Related Macular Degeneration

Ilex paraguariensis Extracts Prevent Oxidative Damage in a Mouse Model of Age‐Related Macular Degeneration

A High Fat “Western‐style” Diet Induces AMD‐Like Features in Wildtype Mice

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