Neuronal and vascular retinal dysfunction on the stages of disease progression in a new experimental model of metabolic syndrome?.

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

Montreal

Congreso; ISN/ASN 2019 Annual Meeting (International Society of Neurochemistry and the American Society of Neurochemistry).; 2019

International Society of Neurochemistry and the American Society of Neurochemistry

Background: Diabetic retinopathy (DR) is the most seriousocular complication associated with T2DM, which is a metabolicsyndrome (MS), and one of the leading causes of secondaryblindness. Although animal models of DR have helped to advance inthe knowledge of this disease, these models have some limitations toreproduce completely the early stage where take place the beginningof the neuronal and vascular alteration.Objetive: Analyze in early stages of the MS, markers of retinalvascular integrity and neuronal functionality to explore details of themechanisms of action that command this event.Materials and Methods: Animals, C57BL/6 (WT) andApolipoprotein E knockout mice (ApoE-KO) either fed with anormal diet (ND) or a 10% w/v fructose diet (FD) in drinking waterfrom 2 months of age. Time-dependent kinetic studies were donefrom 4 to 6 months of age analyzing lipid and glucose metabolicparameters, glucose tolerance test (GTT) and insulin tolerance test(ITT), Total, LDL and HDL Cholesterol, Triglycerides, amongothers. All groups animals (n = 8 per group) for GTTs, were fasted5 h prior to 2 g/kg body weight IP injection of glucose or 0.75U/kgbody weight IP of regular human insulin for ITTs. Blood sampleswere taken from the tail vein at time 0 before injection and at 0.5; 1and 2 h after this. Retinal functionality was assessed by electroretinography(ERG) at 2, 3 and 4 month of treatment in micefully dark-adapted overnight ( > 15 h). The specify markerexpression of retinal neuronal integrity or degenerative damagewas evaluated by Western Blot. Retinal histology and immunofluorescence(IF) analysis were performed in flatmounts and cryosections,whereas vascular permeability and leakage were quantified byEvans Blue extravasations. GraphPad Prism program was employedfor statistical analysis.Results: After 2 month of treatment, ApoE-KO FD miceshowed, in addition to dyslipidemic profile, altered GTT and ITTas compared with the other groups. At this time, the ERG a- and bwavedid not show changes but the oscillatory potential (OPs)amplitudes were significantly decrease in retinas of these micecompared to ApoE-KO ND mice (pConclusion: The results showedthat ApoE-KO mice after 2 months of taking fructose presentedmetabolic alterations mimicking some features of human MS at itsinitial stages of the DR. Thus, this model could offer the benefit toinvestigate DR at an early stage of the MS, where the beginning ofneuronal and vascular retinal dysfunction take place. This representa big opportunity to apply different therapeutic strategy at differenttime point to the traditional.