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Peter F. Kador, Peng Zhang; Effects Of Glucose And Galactose On Comparative Changes Of Growth Factors And Mapk Signaling Of Rat Retinal Capillary Cells.. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2420.
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© ARVO (1962-2015); The Authors (2016-present)
In rat lenses growth factor and signaling changes do not directly result from the presence of diabetes or sorbitol/galactitol (polyol) formation/accumulation, but from secondary osmotic changes associated with the aldose reductase (AR) catalyzed polyol formation. While AR is present in both rat pericytes and endothelial cells, significant polyol formation linked to apoptosis only occurs in pericytes. The purpose of this study was to determine the effects of high glucose/galactose media and polyol formation on growth factor and signaling changes in the rat capillary cells.
Conditionally immortalized rat retinal pericyte (TR-rPCT) and endothelial (TR-iBRB) cell lines were cultured on collagen type 1 coated dishes in DMEM medium containing 5.5 mM glucose. After 24 hours of initial culture, the medium was replaced with serum free medium containing 5.5, 25 or 50 mM glucose or galactose with/without the aldose reductase inhibitors(ARIs) AL1576 or tolrestat for periods of up to 48 hours. Growth factors and transduction pathways were measured by Western blots using the antibodies against basic-FGF, IGF-1, TGF-β, P-ERK1/2, P-SAPK/JNK, and P-Akt.
Sorbitol accumulation was only observed in pericytes while galactitol was present in both pericytes and endothelial cells. Pericytes cultured in high glucose showed increased expression of basic-FGF, IGF-1, TGF-β, P-Akt, P-ERK1/2 and P-SAPK/JNK compared to those cultured in 5.5 mM glucose and the presence of ARIs reduced these expressions. Similar results were observed with galactose media. In contrast, endothelial cells cultured in high glucose media showed increased expression of basic-FGF, P-Akt, and P-SAPK/JNK which were not normalized with ARIs. In galactose media endothelial cells showed increased expression of basic-FGF, IGF-1, TGF-β, P-ERK1/2 and P-SAPK/JNK which were only partially reduced by ARIs.
Growth factor (basic-FGF, IGF-1, TGF-β) and MAPK signaling (P-Akt, P-ERK1/2, P-SAPK/JNK) expressions are linked to the presence of polyols. Pericytes which readily accumulate sorbitol/galactitol that is inhibited by ARIs showed expression changes similar to those observed in rat lenses. In contrast, endothelial cells showed partial expression changes in b-FGF, IGF, TGF-β, P-ERK1/2 and P-SAPK/JNK linked to galactitol accumulation.
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