Neuronal functionality and vascular integrity alteration in retina of mouse metabolic syndrome model triggered by long term fructose intake.

PAZ MC; RIDANO MAGALI E; SANCHEZ MC; BARCELONA PF; CASTRO C; SUBIRADA CALDARONE PAULA; CHIABRANDO GA

Congreso; XXXIV Congreso Anual de Sociedad Argentina de Investigación en Neurociencias; 2019

Type 2 Diabetes mellitus is consequence of the metabolic syndrome (MS), being diabetic retinopathy (DR) a serious complication and cause of blindness in the worldwide. 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 glucouse intolerance. 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 behavior of the MGCs. However, GFAP immunoreactivity decreased was observed in ApoE-KO mice in retinal flatmounts, which could explain the reduced integrity of the blood-retinal barrier. The expression of HIF VEGF, TNF-α and IL-6 mRNA, was not modified in ApoE-KO FD, reinforcing that the changes observed at the time evaluated are associated with early stages of RD. The autophagy mechanism was evaluated, observing no changes of LC3, p62 expression in ApoE-KO DF vs. an increase in WT FD and ApoE-KO ND, which could explain the higher cell death in retina of ApoE-KO FD mice.The results showed that the ApoE-KO DF mice present biochemical alterations characteristics of human MS, with deleterious implications on retinal function and blood-retinal barrier integrity, as well as on intracellular recycling mechanisms. Therefore, this model offers the opportunity to study early stages of the DR , whose prevalence increases in the worldwide.