The retinal oxysterol pathway: a unifying hypothesis for the cause of age-related macular degeneration

Javitt, Norman B.; Javitt, Jonathan C.

doi:10.1097/icu.0b013e32832af468

Cited by 43 publications

(37 citation statements)

References 26 publications

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“…In early AMD, the complement components and acute-phase proteins deposited in drusen44 and BLamD45 may recruit macrophages to BrM and promote phagocytosis. Accumulation of oxidised cholesterol, a by-product of photoreceptor function, in drusen and BLinD may directly attract macrophages and promote vascular endothelial growth factor (VEGF) expression 46. Recruited macrophages may also contribute to, or alter, the biochemical composition of drusen or BLamD 47.…”

Section: Discussionmentioning

confidence: 99%

Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration

Cherepanoff

McMenamin

Gillies

et al. 2009

British Journal of Ophthalmology

218

169

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Section: Discussionmentioning

confidence: 99%

Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration

Cherepanoff

McMenamin

Gillies

et al. 2009

British Journal of Ophthalmology

218

169

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“…This may lead to dysfunction and injury at the histological level, resulting in the development or exacerbation of several pathological conditions. Indeed, oxysterols have been implicated in atherosclerosis (3,7,20), Alzheimer's disease (14,18), age-related macular degeneration (8,9,15), and Parkinson's disease (2).…”

mentioning

confidence: 99%

7-Ketocholesterol Catabolism by Rhodococcus jostii RHA1

Mathieu

Mohn

Eltis

et al. 2010

Appl Environ Microbiol

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Oxysterols from steroid autooxidation have numerous harmful effects, but their biodegradation is poorly understood. Microarrays were used to study mineralization of the most common oxysterol, 7-ketocholesterol (7KC), by Rhodococcus jostii RHA1. Growth on 7KC versus growth on cholesterol resulted in 363 differentially expressed genes, including upregulation of two large gene clusters putatively encoding steroid catabolism. Despite this difference, 7KC degradation required key genes involved in cholesterol degradation, indicating a common catabolic route.

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“…It also acts as an attractant for macrophages to induce inflammation. 55 Because of documented lipofuscin phototoxicity, targeting lipofuscin and the visual cycle has been proposed as an approach for treating AMD.…”

Section: Lipofuscin and Visual Cycle Inhibitorsmentioning

confidence: 99%

Current therapeutic developments in atrophic age-related macular degeneration

2015

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Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease.

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The retinal oxysterol pathway: a unifying hypothesis for the cause of age-related macular degeneration

Abstract: The toxic role of 7-ketocholesterol and existing pathways for its neutralization may point the way to a unified theory that explains the cause of age-related macular degeneration and points towards novel therapeutic interventions.

Cited by 43 publications

References 26 publications

Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration

Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration

7-Ketocholesterol Catabolism by Rhodococcus jostii RHA1

Current therapeutic developments in atrophic age-related macular degeneration

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