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P. Yong, A. Stitt, T. Curtis; The Advanced Lipoxidation End-Product, FDP-Lysine, Preferentially Accumulates in Retinal Müller Cells During Diabetes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5898.
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To investigate the cellular localization and temporal accumulation of advanced lipoxidation end-products (ALEs) in the retina during early experimental diabetes. The ability of pyridoxamine (PM), an ALE inhibitor, to prevent ALE accumulation was also evaluated.
The specificity of antibodies directed against Nε-(3-formyl-3,4-dehydropiperidino)lysine (acrolein-derived ALE; FDP-lysine) and 4-hydroxy-2-nonenal histidine (HNE) adducts were assessed by western dot blot analysis and used for immunohistochemical staining of retinal sections from control (n=6), streptozotocin(STZ)-induced diabetic rats (n=6) and diabetic animals treated with pyridoxamine (1 g/l drinking water; n=5). Sections were examined using confocal microscopy and fluorescence intensities of different layers of the retina were semiquantitatively analysed.
Levels of 4-HNE modified proteins were similar in the retinas of control and diabetic animals after 4-months of diabetes (p>0.05). By contrast, a progressive accumulation of FDP-lysine was observed within the ganglion cell and inner plexiform layers of diabetic rats between 2-4 months disease-duration (p<0.05 at 2-months, p<0.001 at 4-months). During diabetes, Müller cells are known to exhibit intense expression of glial fibrillary acidic protein (GFAP), which is almost completely downregulated in retinal astrocytes (Barber et al, IOVS, 2000, 41:3561-8). In diabetic rats, FDP-lysine colocalised extensively with GFAP suggesting that this adduct selectively accumulates in Müller cells during diabetes. PM protected diabetic rats of 4-months disease duration from Müller cell accumulation of FDP-lysine (p>0.05 versus controls).
Acrolein-derived ALEs accumulate preferentially in Müller cells during early diabetes. PM may prevent the accumulation of ALEs in the diabetic retina. Acrolein-derived ALEs might be one of the factors that contribute to the reactive gliosis reported in the early stages of diabetic retinopathy.
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