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

SUBIRADA, PV; CHIABRANDO GA; PAZ, MC; RIDANO, ME; SANCHEZ, MC; BARCELONA PF; CASTRO, C

Mar del Plata

Congreso; SAIC 2018 LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

SAIC

Diabetes mellitus type 2 is consequence of the metabolic syndrome (MS), being diabetic retinopathy (RD) a serious complication and cause of blindness in the world. We aimed to analyze markers of vascular integrity and neuronal functionality related to early stages of DR in a model of MS.C57BL/6 (WT) and Apolipoprotein E knockout (ApoE-KO) mice fed with a normal diet (ND) or a 10% w/v fructose diet (FD) in drinking water from 2 months of age, were used. Time-dependent kinetic studies were done from 2 to 6 months of diet.The hypercholesterolemic ApoE-KO showed an increase in LDL-Chol, and being fed with FD, they also showed hypertriglyceridemia and a decrease in HDL-Chol, in addition to hyperglycemia, hyperinsulinemia and an altered glucouse tolerance test. The scotopic ERG showed a decrease in a, b waves and in OPs of ApoE-KO DF vs WT DN, which correlated with an increase in TUNEL positive cells. A high vascular permeability in ApoE-KO FD was evidenced by the leakage of Evans blue (e.v.) and the extravasation of albumin and α2-Macroglobulin. GFAP expression were observed in astrocytes but not in Müller glial cells (MGCs), so there is no reactive gliosis in retinas of ApoE-KO FD, which correlates with the normal expression of the glutamine synthetase, indicating a normal operation of the MGCs. However, a decrease in GFAP immunoreactivity was observed in retinal 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, which reproduce characteristics of the human SM, presented vascular dysfunction and neurodegeneration, without alterations related to tissue ischemia. Therefore, this model offers the opportunity to study early stages of the DR, whose prevalence increases in the world.