title: Dietary glycotoxins induce RAGE and VEGF up-regulation in the retina of normal rats.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece.
authors.forename: Stylianos A
authors.initials: SA
authors.lastname: Kandarakis
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Moschonas
authors.affiliation: 1st Department of Pathology, University of Athens Medical School, 11527 Athens, Greece.
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.affiliation: Experimental-Research Center, ELPEN Pharmaceuticals, 19009 Pikermi, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece. Electronic address: papavas@med.uoa.gr.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D017127:Glycation End Products, Advanced; D042461:Vascular Endothelial Growth Factor A
keywords: Advanced glycation end products; Glycotoxins; Ocular tissues; RAGE; VEGF-A