Extra-hepatic metabolism of 7-ketocholesterol occurs by esterification to fatty acids via cPLA2α and SOAT1 followed by selective efflux to HDL.

Accumulation of 7-ketocholesterol (7KCh) in tissues has been previously associated with various chronic aging diseases. Orally ingested 7KCh is readily metabolized by the liver and does not pose a toxicity threat. However, 7KCh formed in situ, usually associated with lipoprotein deposits, can adversely affect surrounding tissues by causing inflammation and cytotoxicity.

7-Ketocholesterol-induced inflammation signals mostly through the TLR4 receptor both in vitro and in vivo.

The cholesterol oxide 7-ketocholesterol (7KCh) has been implicated in numerous age-related diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer and age-related macular degeneration. It is formed by the autooxidation of cholesterol and especially cholesterol-fatty acid esters found in lipoprotein deposits. This molecule causes complex and potent inflammatory responses in vitro and in vivo.

Sterculic acid antagonizes 7-ketocholesterol-mediated inflammation and inhibits choroidal neovascularization.

Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration.

Passage of low-density lipoproteins through Bruch's membrane and choroid.

Plasma lipoproteins are thought to transport cholesterol, vitamins and carotenoids to the retinal pigment epithelium (RPE) for ultimate use by the photoreceptors. However, to reach the RPE, these lipoprotein particles must cross Bruch's membrane. We examined the reflection coefficient of Bruch's membrane (BrM) to low-density lipoprotein (LDL).

The oil spill in ageing Bruch membrane.

Ageing is the largest risk factor for age-related macular degeneration (AMD), and soft drusen and basal linear deposits are lipid-rich extracellular lesions specific to AMD. Oil red O binding neutral lipid represents a major age-related deposition in the Bruch membrane (BrM) and the first identified druse component. Decades after these seminal observations, a natural history of neutral lipid deposition has been articulated and a biochemical model proposed.

Adequacy of exchanging the content of the anterior chamber.

Perfusion studies of the anterior segment of the eye frequently involve an exchange of the contents of the anterior chamber. We here determined how much fluid was necessary to pass through the upstream tubing and anterior chamber such that the contents of the anterior chamber were adequately exchanged. We used fluorescein dextran (500 kD) to assess the adequacy of exchange of enucleated porcine eyes that were washed out with varying volumes of buffer.

7-ketocholesterol-induced inflammation: involvement of multiple kinase signaling pathways via NFκB but independently of reactive oxygen species formation.

Purpose: 7-Ketocholesterol (7KCh) accumulates in oxidized lipoprotein deposits and is known to be involved in macrophage foam cell formation and atherosclerosis. 7-KCh is present in the primate retina and is associated with oxidized lipoprotein deposits located in the choriocapillaris, Bruch's membrane, and retinal pigment epithelium (RPE). 7-KCh can also be formed in the retina as a consequence of light-induced iron release.

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration.

The largest risk factor for age-related macular degeneration (ARMD) is advanced age. With aging, there is a striking accumulation of neutral lipids in Bruch's membrane (BrM) of normal eye that continues through adulthood. This accumulation has the potential to significantly impact the physiology of the retinal pigment epithelium (RPE).

Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins.

The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch's membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE).

Morphometric analysis of lipoprotein-like particle accumulation in aging human macular Bruch's membrane.

Purpose: To determine the size and regional distribution of lipoprotein-like particles (LLPs) that accumulate with age in Bruch's membrane (BrM).

Methods: The quick-freeze/deep-etch method was used to prepare specimens of human BrM (age range, 27-78) for electron microscopic examination. Stereologic methods were used to analyze the resultant micrographs and determine the age-related changes of the LLP volume fraction and diameter distribution in various locations in BrM.

Comparison of morphology of human macular and peripheral Bruch's membrane in older eyes.

Deposits in macular human Bruch's membrane (BrM) increase with age and have been postulated to be associated with age-related maculopathy. We used two ultrastructural methods to compare these deposits by electron microscopy in macular and peripheral BrM of eight eyes from donors 63-86 years of age. Quick-freeze/deep-etch (QFDE) was used to prepare replicas that showed the ultrastructure of deposits, and osmium-tannic acid-paraphenylenediamine (OTAP) was used to preserve small extracellular lipid particles.

Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch.

Lipid-containing inclusions have been observed in human Bruch's membrane (BrM) and are postulated to be associated with age-related maculopathy (ARM), a major cause of legal blindness in developed countries. The dehydration associated with specimen preparation for thin-section transmission electron microscopy causes loss of these inclusions. Better preservation of the ultrastructure of the inclusions and tissue is achieved by using a quick-freeze/deep-etch preparation.

Quick-freeze/deep-etch visualization of age-related lipid accumulation in Bruch's membrane.

Purpose: To examine age-related changes in the ultrastructure of Bruch's membrane with quick-freeze/deep-etch (QFDE) and conventional thin-section transmission electron microscopy (TEM).

Methods: Four eyes from human donors aged 27, 41, 76, and 78 years were preserved within 4 hours of death. Full-thickness tissue blocks from the macula were prepared for TEM or for QFDE.