Neuronal functionality and vascular integrity alterations in retina of a mouse metabolic syndrome model triggered by long-term fructose intake

PAULA V. SUBIRADA; CLAUDIA CASTRO; MARIA C. PAZ; MAGALI E. RIDANO; MARIA C. SANCHEZ; PABLO F. BARCELONA; GUSTAVO CHIABRANDO

Carlos Paz, Cordoba

Congreso; XXXIV Annual Meeting of SAN (Sociedad Argentina de Investigación en Neurociencia); 2019

Sociedad Argentina de Investigación en Neurociencias

Type 2 diabetes is consequence of metabolic syndrome (MS), being diabetic retinopathy (DR) a serious complication and cause of blindness in 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 (ApoEKO) mice fed with normal diet (ND) or 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.Hypercholesterolemic ApoEKO mice showed an increase in LDL-Chol, and being fed with FD, showed hypertriglyceridemia and decreased HDL-Chol, as well as hyperglycemia, hyperinsulinemia and glucouse intolerance. Scotopic ERG showed decreased a, b waves and OPs in ApoEKO FD vs WT DN, which correlated with increased TUNEL positive cells. High vascular permeability in ApoEKO 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 ApoEKO FD, which correlates with normal expression of the GS, indicating normal behavior of the MGCs. However, GFAP immunoreactivity decreased in ApoEKO FD retinal flat mounts, which could explain the reduced integrity of BRB. The expression of HIF, VEGF, TNFα and IL6 mRNA, was not modified in ApoEKO FD, reinforcing the changes observed are associated with early stages of DR. Autophagy mechanism was evaluated, observing no changes of LC3 and p62 expression in ApoEKO FD vs increase in WT FD and ApoEKO ND, which could explain higher cell death in ApoEKO FD retinas.The results showed ApoEKO FD mice present biochemical alterations of MS, with deleterious implications on retinal function and BRB integrity, as well as on intracellular recycling mechanisms. ApoEKO FD mice could be useful for analyze pathogenic mechanisms of RD, as well as a possible platform for therapeutic strategies.