Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Invest Ophthalmol Vis Sci. 2011 Feb 1;52(1):594-603. doi: 10.1167/iovs.10-6021. Print 2011 Jan.
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.
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.
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.
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.
越来越多的证据表明胆固醇与年龄相关性黄斑变性之间存在关联。然而，对于胆固醇从视网膜和视网膜色素上皮（RPE）中清除的机制知之甚少，而这两层组织正是这种致盲性疾病的损伤部位。在眼外组织中存在几种不同的酶促胆固醇清除途径。作者测试了这些途径的代谢产物是否也可以在牛和人视网膜和 RPE 中定量。为了进行比较，他们还测量了牛和人脑中两个区域以及牛肝和肾上腺中胆固醇氧化产物的含量。
固醇定量采用同位素稀释气相色谱-质谱法进行。首先使用牛组织来优化分析程序，并研究牛组织中氧化固醇浓度的死后变化。然后分析人标本中的氧化固醇浓度。
定性分析表明，牛和人组织中的氧化固醇谱相似。在人视网膜和 RPE 中，作者无法检测到 27-羟胆固醇，但出人意料地发现，其氧化产物 5-胆甾烯酸是最丰富的氧化固醇，在不同个体中变化高达三倍。24S-羟胆固醇和孕烯醇酮也存在于视网膜中，但数量要低得多，且个体间差异不显著。在大脑中，主要的氧化固醇是 24S-羟胆固醇。
视网膜中的氧化固醇谱表明，所有已知的眼外器官胆固醇消除途径在视网膜中均起作用，并且它们可能根据特定的细胞类型而变化。然而，总体上氧化为 5-胆甾烯酸似乎是从该器官中清除胆固醇的主要机制。
