Metabolic Syndrome triggered by high-fructose diet shows vascular integrity and neuronal functionality alterations in mouse retina

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

Mar del Plata

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

Sociedad Argentina de Investigación Clínica (SAIC)

Type 2 Diabetes mellitus 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 altered glucouse tolerance test. Scotopic ERG showed decreased a, b waves and OPs in ApoE-KO DF vs WT DN, which correlated with increased TUNEL positive cells. High vascular permeability in ApoE-KO FD was evidenced by leakage of Evans blue (e.v.) and 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 normal expression of the glutamine synthetase, indicating a normal operation of the MGCs. However, GFAP immunoreactivity decreased 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.