ALTERATIONS IN VASCULAR INTEGRITY AND NEURONAL FUNCTIONALITY RELATED TO EARLY STAGES OF DIABETIC RETINOPATHY IN A METABOLIC SYNDROME MOUSE MODEL

PAZ, MARÍA C.; BARCELONA PF; SUBIRADA CALDARONE, PAULA V.; RIDANO M; CASTRO C; CHIABRANDO GA; SÁNCHEZ MC

Ciudad Autónoma de Buenos Aires

Congreso; Reunion conjunta de Sociedades de Biociencias; 2017

SAIB en conjunto con 10 sociedades científicas en biociencias del país.

Diabetic retinopathy (DR) is the most serious ocular complicationassociated with Type 2 Diabetes Mellitus (T2DM), which is a metabolicsyndrome (MS), and one of the leading causes of blindness.Thus, we proposed to analyze in a MS mouse model, markers ofretinal vascular integrity and neuronal functionality, related to earlystages of DR.We used C57BL/6 (WT) and Apolipoprotein E knockout (ApoEKO)mice either fed with a normal diet (ND) or a 10% w/v fructosediet (FD) in drinking water from 2 months of age. We demonstratedApoE-KO after 2 month of FD, presented hypercholesterolemia,hypertriglyceridemia, hyperglycemia and hyperinsulinemia. Here,retinal functionality was assessed by scotopic ERG at 4 month ofFD treatment. Extravasation of serum proteins and levels of proteinsinvolved in neuro-glial injury were analyzed by WB. Vascular permeabilitywas evaluated by albumin?Evans blue complex leakage andastrocyte GFAP levels on whole mounts of retina.The ERG a-wave and the OPs amplitudes were significantlydecreased in retinas of ApoE-KO after 4 month of FD vs WT DN(p<0.05), correlating with an increase in TUNEL positive cells. Highervascular permeability was observed in ApoE-KO FD, evidencedby the Evans blue leakage and the albumin and α2-M extravasation.At this early stage of the DR, the GFAP expression levelswere observed just in astrocytes but not in Müller glial cells (MC)demonstrating non-reactive gliosis in retinas of ApoE-KO FD, whichcorrelated with the GS expression pointing out a normal function ofMC. However, a reduction in GFAP immunoreactivity was observedin ApoE-KO FD whole mounts, which may be linked to a reduced ability to maintain BRB characteristics in ECs.The results showed that ApoE-KO after 4 months of FD, which representfeatures of human MS, presented vascular dysfunction andneurodegeneration. Thus, this model could offer the opportunity toinvestigate DR at an early stage, whose prevalence has increasedsubstantially worldwide.