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

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

Congreso; XXXIV Congreso Anual de Sociedad Argentina de Investigación en Neurociencias (SAN); 2019

Type 2 diabetes is consequence of metabolic syndrome (MS), being diabetic retinopathy (DR) a seriouscomplication and cause of blindness in worldwide. We aimed to analyze markers of vascular integrity andneuronal 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 6months of diet.Hypercholesterolemic ApoEKO mice showed an increase in LDL-Chol, and being fed with FD, showedhypertriglyceridemia and decreased HDL-Chol, as well as hyperglycemia, hyperinsulinemia and glucouseintolerance. Scotopic ERG showed decreased a, b waves and OPs in ApoEKO FD vs WT DN, which correlated withincreased 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 notin Müller glial cells (MGCs), so there is no reactive gliosis in retinas of ApoEKO FD, which correlates with normalexpression of the GS, indicating normal behavior of the MGCs. However, GFAP immunoreactivity decreased inApoEKO 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 earlystages of DR. Autophagy mechanism was evaluated, observing no changes of LC3 and p62 expression in ApoEKOFD 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 onretinal function and BRB integrity, as well as on intracellular recycling mechanisms. ApoEKO FD mice could beuseful for analyze pathogenic mechanisms of RD, as well as a possible platform for therapeutic strategies.