Cholestenoic Acid is an important elimination product of cholesterol in the retina: comparison of retinal cholesterol metabolism with that in the brain.
OBJECTIVE
Accumulating evidence indicates a link between cholesterol and age-related macular degeneration. Yet, little is known about cholesterol elimination from the retina and retinal pigment epithelium (RPE), the two layers that are damaged in this blinding disease. Several different pathways of enzymatic cholesterol removal exist in extraocular tissues. The authors tested whether metabolites from these pathways could also be quantified in the bovine and human retina and RPE. For comparison, they measured cholesterol oxidation products in two regions of the bovine and human brain and in the bovine liver and adrenal glands.


METHODS
Sterol quantification was carried out by isotope dilution gas chromatography-mass spectrometry. Bovine tissues were used first to optimize analytical procedures and to investigate postmortem changes in oxysterol concentrations. Then human specimens were analyzed for oxysterol concentrations.


RESULTS
Qualitatively, oxysterol profiles were similar in the bovine and human tissues. In the human retina and RPE, the authors could not detect 27-hydroxycholesterol but unexpectedly found that its oxidation product, 5-cholestenoic acid, is the most abundant oxysterol, varying up to threefold in different persons. 24S-Hydroxysterol and pregnenolone were also present in the retina, but at much lower quantities and without significant interindividual variability. In the brain, the predominant oxysterol was 24S-hydroxycholesterol.


CONCLUSIONS
The oxysterol profile of the retina suggests that all known pathways of cholesterol elimination in extraocular organs are operative in the retina and that they likely vary depending on specific cell type. However, overall oxidation to 5-cholestenoic acid appears to be the predominant mechanism for cholesterol elimination from this organ.
Mast
Natalia
N
Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Reem
Rachel
R
Bederman
Ilya
I
Huang
Suber
S
DiPatre
Pier Luigi
PL
Bjorkhem
Ingemar
I
Pikuleva
Irina A
IA
D000311:Adrenal Glands / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D053493:Cholestanetriol 26-Monooxygenase / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism*; D000072556:Cholesterol 24-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism
D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C029435:3-hydroxy-5-cholestenoic acid; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase; D053493:Cholestanetriol 26-Monooxygenase; D002786:Cholesterol Side-Chain Cleavage Enzyme