METABOLIC SYNDROME TRIGGERED BY HIGH-FRUCTOSE DIET SHOWS VASCULAR INTEGRITY AND NEURONAL FUNCTIONALITY ALTERATIONS IN MOUSE RETINA

PAZ, MARÍA C.; BARCELONA, PABLO F.; SUBIRADA CALDARONE, PAULA V.; RIDANO, MAGALI E.; CHIABRANDO GUSTAVO; CASTRO CLAUDIA; SÁNCHEZ MARÍA CECILIA

Mar del Plata

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación Clínicas (SAIC); 2018

SAIC

Diabetes mellitus type 2 is consequence of the metabolicsyndrome (MS), being diabetic retinopathy (RD) a seriouscomplication and cause of blindness in the world.We aimed to analyze markers of vascular integrity andneuronal functionality related to early stages of DR in amodel of MS.C57BL/6 (WT) and Apolipoprotein E knockout (ApoEKO)mice fed with a normal diet (ND) or a 10% w/v fructosediet (FD) in drinking water from 2 months of agewere used. Time-dependent kinetic studies were donefrom 2 to 6 months of diet.The hypercholesterolemic ApoE-KO showed an increasein LDL-Chol, and being fed with FD, they also showedhypertriglyceridemia and a decrease in HDL-Chol, inaddition to hyperglycemia, hyperinsulinemia and alteredglucouse tolerance test. Scotopic ERG showeddecreased a, b waves and OPs in ApoE-KO DF vs WTDN, which correlated with increased TUNEL positive cells. High vascular permeability in ApoE-KO FD was evidencedby leakage of Evans blue (e.v.) and extravasation of albumin and a2-Macroglobulin. GAFP expression was observed in astrocytes but not in Müller glial cells (MGCs), so there is no reactive gliosis in retinas of ApoEKO FD, which correlates with normal expression of the glutamine synthetase, indicating a normal operation of the MGCs. However, GFAP immunoreactivity decreased was observed in retinas flatmounts, which could explain the reduced integrity of the blood-retinal barrier. The expression of HIF and VEGF mRNA was not modified in any group, indicating changes associated with early stages of RD, without characteristics related to stages of neovascularization, at the time evaluated.The results showed that the ApoE-KO DF mice, whichreproduce characteristics of the human SM, presentedvascular dysfunction and neurodegeneration, without alterationsrelated to tissue ischemia. Therefore, this modeloffers the opportunity to study early stages of the DR,whose prevalence increases in the world.