7-ketocholesterol accumulates in ocular tissues as a consequence of aging and is present in high levels in drusen

Academic Article

Abstract

  • © 2014. We analyzed by LCMS lipid extracts of lens, retina (MNR) and RPE/Choroid (MPEC) from macaque monkeys 2-25yr 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 72-95yr. The lowest 7KCh levels were found in monkey lens (<0.5-3.5pmol 7KCh per nmol Ch), the second highest in MNR (1-15pmol/nmol), and the highest in MPEC (1 to >60pmol/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 20pmol/nmol, similar to the oldest monkeys, but 7-KCh levels in RPE ranged from 200 to 17,000pmol/nmol, and in RPE-capped drusen from 200 to 2000pmol/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.
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    Digital Object Identifier (doi)

    Author List

  • Rodriguez IR; Clark ME; Lee JW; Curcio CA
  • Start Page

  • 151
  • End Page

  • 155
  • Volume

  • 128