Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6196781 | Experimental Eye Research | 2014 | 5 Pages |
We analyzed by LCMS lipid extracts of lens, retina (MNR) and RPE/Choroid (MPEC) from macaque monkeys 2-25Â yr in age to determine their content of 7-ketocholesterol (7KCh) as function of age. In addition we also analyzed drusen capped with retinal pigment epithelium (RPE), RPE, and neural retina from human donors age 72-95Â yr. The lowest 7KCh levels were found in monkey lens (<0.5-3.5Â pmol 7KCh per nmol Ch), the second highest in MNR (1-15Â pmol/nmol), and the highest in MPEC (1 to >60Â pmol/nmol). Despite individual variability all three tissues demonstrated a strong age-related increase. In older human donors 7KCh levels were significantly higher. The levels in human neural retina ranged from 8 to 20Â pmol/nmol, similar to the oldest monkeys, but 7-KCh levels in RPE ranged from 200 to 17,000Â pmol/nmol, and in RPE-capped drusen from 200 to 2000Â pmol/nmol, levels that would be lethal in most cultured cell systems. Most of the 7KCh is sequestered and not readily available to the surrounding tissue, based on published histochemical evidence that extracellular cholesterol (Ch) and cholesteryl fatty acid esters (CEs) are highly concentrated in Bruch's membrane and drusen. However, adjacent tissues, especially RPE but also choriocapillaris endothelium, could be chronically inflamed and in peril of receiving a lethal exposure. Implications for initiation and progression of age-related macular degeneration are discussed.