"Catalyzed by iron"
Cholesterol oxidation in the retina: Implications of 7-ketocholesterol
formation in
chronic inflammation and age-related macular degeneration.
Rodriguez IR, Larrayoz IM.
J Lipid Res. 2010 Jun 21.
National Eye Institute, NIH, United States.
Abstract
This review will discuss the formation and potential implications of 7-
ketocholesterol
(7KCh) in the retina.
7KCh is a pro-inflammatory oxysterol known to be present in high
amounts in oxidized
low density lipoprotein deposits associated with atheromatous
plaques.
7KCh is generated in situ in these lipoprotein deposits where it can
accumulate and
reach very high concentrations.
In normal primate retina 7KCh has been found associated with
lipoprotein deposits in
the choriocapillaris, Bruch's membrane and the retinal pigment
epithelium (RPE).
In photodamaged rats, 7KCh has been found in the neural retina in
areas of high
mitochondrial content, ganglion cells, photoreceptor inner segments
and synapses
and the RPE.
Intermediates found by LCMS indicate 7KCh is formed via a free radical
mediated
mechanism catalyzed by iron.
7KCh seems to activate several kinase signaling pathways that work via
NFkappaB
and cause the induction of VEGF, IL-6 and IL-8.
There seems to be little evidence of 7KCh metabolism in the retina
although some
form of efflux mechanism may be active.
The chronic mode of formation and the potent inflammatory properties
of 7KCh
indicate it may be an ''age-related'' risk factor in aging diseases
such as atherosclerosis,
Alzheimer's and age-related macular degeneration.
PMID: 20567027
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