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Timothy J. Lyons, Wei Li, Barbara Wojciechowski, Mary C. Wells–Knecht, Kevin J. Wells–Knecht, Alicia J. Jenkins; Aminoguanidine and the Effects of Modified LDL on Cultured Retinal Capillary Cells. Invest. Ophthalmol. Vis. Sci. 2000;41(5):1176-1180.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. Compared with normal low density lipoprotein (N–LDL), LDL minimally
modified in vitro by glycation, minimal oxidation, or glycoxidation
(G–, MO–, GO–LDL) decreases survival of cultured retinal capillary
endothelial cells and pericytes. Similar modifications occurring in
vivo in diabetes may contribute to retinopathy. The goal of
this study was to determine whether low concentrations of
aminoguanidine might prevent cytotoxic modification of LDL and/or
protect retinal capillary cells from previously modified LDL.
methods. Minimal in vitro modification of LDL (3 days, 37°C) was achieved with
glucose (0, 50 mM), under antioxidant conditions (for N–LDL, G–LDL),
or under mild oxidant conditions (for MO–, GO–LDL) in the
presence/absence of aminoguanidine (0, 1, 10, 100 μM). Glucose and
aminoguanidine were then removed by dialysis. Confluent bovine retinal
capillary endothelial cells (n = 13) and pericytes
(n = 14) were exposed to LDL (100 mg/l) for 3 days,
with and without aminoguanidine (100 μM) in media. Cell counts were
determined by hemocytometer.
results. A decrease in cell counts after exposure to modified compared
with N–LDL was confirmed (P < 0.001) but was
significantly mitigated if LDL had been modified in the presence of
aminoguanidine (P < 0.001). Aminoguanidine was as
effective at 1 μM as at the higher concentrations. Aminoguanidine
(100 μM) present in culture media conferred no additional protection,
and showed slight evidence of toxicity. Aminoguanidine present during
LDL modification had no effect on measured glycation or oxidation
products, or on LDL oxidizability.
conclusions. Very low concentrations of aminoguanidine mitigate toxicity of LDL
exposed to stresses that simulate the diabetic environment. This action
may contribute to the beneficial effects of aminoguanidine observed in
experimental diabetic retinopathy.
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