Oxidized low density lipoproteins induce a pathologic response by retinal pigmented epithelial cells

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Accumulation of apolipoprotein B100 lipoproteins in Bruch membrane is an early event in age-related macular degeneration (AMD).
• Oxidized low-density lipoproteins (oxLDL) are implicated in AMD pathogenesis.

Purpose of the Study:

• To investigate the pathological effects of low-density lipoproteins (LDL) and oxidized LDL (oxLDL) on retinal pigmented epithelial cells.
• To determine if oxLDL initiates early events in AMD.

Main Methods:

• Immunohistochemistry on AMD specimens.
• Treatment of ARPE-19 cells with LDL and oxLDL.
• Gene chip analysis (Affymetrix U133 Plus 2.0).
• Electrospray mass spectrometry.
• TUNEL assay for apoptosis.
• Sphingomyelin synthase inhibition.

Main Results:

• oxLDL, but not LDL, stained Bruch membrane in AMD specimens.
• oxLDL induced significant transcriptional alterations in lipid metabolism, oxidative stress, inflammation, and apoptosis.
• oxLDL increased cellular sphingomyelin, ceramides, and cholesteryl esters.
• oxLDL caused 14.6% apoptosis in ARPE-19 cells, inhibited by 41% with sphingomyelin synthase inhibitor.

Conclusions:

• Oxidized lipoproteins are a key trigger for initiating early events in age-related macular degeneration pathogenesis.
• oxLDL induces cellular changes and apoptosis in retinal pigmented epithelial cells, supporting its role in AMD.