Macular and Plasma Xanthophylls Are Higher in Age-related Macular Degeneration than in Normal Aging

McGwin, Gerald; Kar, Deepayan; Berlin, Andreas; Clark, Mark E.; Swain, Thomas A.; Crosson, Jason N.; Sloan, Kenneth R.; Owsley, Cynthia; Curcio, Christine A.

doi:10.1016/j.xops.2022.100263

Cited by 9 publications

(14 citation statements)

References 85 publications

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“…This mathematical construct is familiar to vision science, because it was used to model excitatory centers and inhibitory surrounds of retinal ganglion cell receptive fields 176 , 177 (i.e., the part of the visual world to which individual neurons respond). Local concentration of xanthophyll carotenoids may be estimable with intensities from two-wavelength autofluorescence and retinal thicknesses from OCT. 16 , 178 , 179 Volumes of drusen at their earliest stages may be determinable automatically from large population-based studies of aging using OCT technology with adequate axial resolution and eye tracking for outer retinal pathology. 72 …”

Section: Cone Resilience and Rod Vulnerability A Center-surround Modelmentioning

confidence: 99%

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Age-Related Macular Degeneration, a Mathematically Tractable Disease

Curcio,

Kar,

Owsley

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.

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Section: Cone Resilience and Rod Vulnerability A Center-surround Modelmentioning

confidence: 99%

“…We can anticipate convergence of tissue-level considerations with AMD genetic associations. A relationship of HDL genes with the xanthophyll bioavailability axis is promising, 179 as is exploration of complement genes in early AMD. 65 , 215 , 216 …”

Section: Strengths Limitations Future Directions and Conclusionmentioning

confidence: 99%

Age-Related Macular Degeneration, a Mathematically Tractable Disease

Curcio,

Kar,

Owsley

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…In this disease process, lipoproteins are deposited as drusen at Bruch’s membrane. It has been hypothesized that supplementation with lutein and zeaxanthin modify high- and low-density lipoproteins, which decreases their uptake by RPE uptake receptors, thereby lowering drusen volume at Bruch’s membrane and the risk for neovascularization in AMD [ 148 ].…”

Section: Age-related Eye Disease and The Role Of Oxidative Stressmentioning

confidence: 99%

The Role of Oxidative Stress in the Aging Eye

Goodman

Ness

2023

Life

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Given the expanding elderly population in the United States and the world, it is important to understand the processes underlying both natural and pathological age-related changes in the eye. Both the anterior and posterior segment of the eye undergo changes in biological, chemical, and physical properties driven by oxidative stress. With advancing age, changes in the anterior segment include dermatochalasis, blepharoptosis, thickening of the sclera, loss of corneal endothelial cells, and stiffening of the lens. Changes in the posterior segment include lowered viscoelasticity of the vitreous body, photoreceptor cell loss, and drusen deposition at the macula and fovea. Age-related ocular pathologies including glaucoma, cataracts, and age-related macular degeneration are largely mediated by oxidative stress. The prevalence of these diseases is expected to increase in the coming years, highlighting the need to develop new therapies that address oxidative stress and slow the progression of age-related pathologies.

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“…The left half of the image shows MPOD distribution in a normative dataset (the black stripe represents the mean value and the grey zones the standard deviation). 9 The right half shows MPOD values obtained from case 1 registered with FAF image of the fundus (mosaic C). Foveal center (radius 0-1°) corresponds to increased optical density values followed by a steep decrease.…”

Section: Case Reportmentioning

confidence: 99%