Advanced Glycation End Products Induce Expression of Vascular Endothelial Growth Factor by Retinal Müller Cells

doi:10.1006/bbrc.1997.7036

Biochemical and Biophysical Research Communications

Volume 236, Issue 3, 30 July 1997, Pages 712-715

https://doi.org/10.1006/bbrc.1997.7036 Get rights and content

Abstract

Recent studies have suggested that advanced glycation end products (AGEs) are involved in the development of diabetic complications. To assess the pathogenic role of AGEs and vascular endothelial growth factor (VEGF) in the development of retinal neovascularization in diabetic retinopathy, we investigated the effect of AGEs on induction of VEGF by retinal Müller cells and measured AGE and VEGF concentrations in the vitreous of patients with proliferative diabetic retinopathy (PDR) and nondiabetic patients. The expression of VEGF mRNA and the production of VEGF protein by cultured Müller cells were enhanced by the presence of AGEs. The vitreous concentrations of AGEs and VEGF were both elevated in patients with PDR compared with patients without diabetes (P< 0.01). There was a moderate positive correlation between the levels of crossline and VEGF (r=0.698,P< 0.01). Elevation of AGEs in the vitreous may promote intraocular neovascularization in diabetic retinopathy through production of VEGF from Müller cells.

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Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats
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Citation Excerpt :
Elevated VEGF expression has been associated to the pathogenesis of neovascularization that underlies diabetic retinopathy and the wet form of macular degeneration, two of the most common causes of blindness worldwide (Rodriguez et al., 2002; Schmidl et al., 2015). A correlation between AGEs and VEGF expression has been previously suggested in diabetic retinopathy (Zong et al., 2011) associated with RAGE signaling (Hirata et al., 1997; Lee et al., 2012; Treins et al., 2001). Taken together this data, we seek to investigate the direct effect of dietary AGEs in the expression of RAGE and VEGF in ocular tissues of normal rats.
Exogenous intake of glycotoxins present in western diet accelerates the accumulation of advanced glycation end products (AGEs) in multiple organs leading to potential tissue damage. Advanced ageing and diabetic conditions have been associated with AGEs deposition in multiple eye compartments including Bruch's membrane, optic nerve, lens and cornea. However, the impact of dietary AGEs in ocular physiology has not been extensively studied. The present study investigates the direct effects of a high AGE content diet in the ocular tissues of normal rats of different age. Two groups of baby (4 weeks of age) and adult (12 weeks of age) female Wistar rats (n = 73) were allocated to high- or low-AGE diet for 3 months. Upon completion of experimental protocol, somatometric, hormonal and biochemical parameters were evaluated in all groups. Circulating and tissue AGE levels were estimated along with their signaling receptor (receptor for AGEs, RAGE) and vascular endothelial growth factor A (VEGF-A) expression in ocular tissues of the different subgroups. High AGE intake was associated with elevated serum AGEs (p = 0.0001), fructosamine (p = 0.0004) and CRP levels (p = 0.0001) compared to low AGE. High peripheral AGE levels were positively correlated with significant increased tissue immunoreactivity of AGEs and RAGE in retinal and uveal tissues as well as retinal VEGF-A expression. Up-regulation of RAGE and VEGF-A expression was observed in the ocular tissue of both baby and adult animals fed with high-AGE diet. Co-localization of AGEs and RAGE staining was observed mainly in the inner retinal layers and the retinal pigment epithelium (RPE) of all groups. VEGF-A expression was elevated in the RPE, the inner nuclear layer and the retinal ganglion cell layer of the animals exposed to high-AGE diet. In conclusion, dietary AGEs intake affects the physiology of ocular tissues by up-regulating RAGE and VEGF-A expression contributing to enhanced inflammatory responses and pathologic neovascularization in normal organisms independent of ageing.
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Advanced glycation end products (AGEs) have been implicated in vision loss associated with macula degeneration, cataract formation, diabetic retinopathy and glaucoma.
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Regular ArticleAdvanced Glycation End Products Induce Expression of Vascular Endothelial Growth Factor by Retinal Müller Cells

Abstract

Biochem. Biophys. Res. Commun.

Am. J. Pathol.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Neuroscience

Lab. Invest.

Arch. Opthalmol.

Invest. Ophthalmol. Vis. Sci.

Science

Regular Article
Advanced Glycation End Products Induce Expression of Vascular Endothelial Growth Factor by Retinal Müller Cells