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

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

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Alterations in vascular integrity and neuronal functionality related to early stages of diabetic retinopathy in a metabolic syndrome mouse model.Paz, MC; Barcelona, PF; Subirada, PV; Ridano, ME; Castro, C; Sánchez, MC.Diabetic retinopathy (DR) is the most serious ocular complication associated with Type 2 Diabetes Mellitus (T2DM), which is a metabolic syndrome (MS), and one of the leading causes of blindness. Thus, we proposed to analyze in a MS mouse model, markers of retinal vascular integrity and neuronal funcionality, related to early stages of DR.We used C57BL/6 (WT) and Apolipoprotein E knockout (ApoE-KO) mice either fed with a normal diet (ND) or a 10% w/v fructose diet (FD) in drinking water from 2 months of age. We demonstrated that ApoE-KO after 2 month of FD, presented hypercolesterolemia, hypertriglyceridemia, hyperglycemia and hyperinsulinemia. Here, retinal functionality was assessed by scotopic ERG at 4 month of FD treatment. Extravasation of serum proteins and levels of proteins involved in neuro-glial injury were analyzed by WB. Vascular permeability was evaluated by albumin?Evans blue complex leakage and astrocyte GFAP levels on whole mounts of retina.The ERG a-wave and the OPs amplitudes were significantly decrease in retinas of ApoE-KO after 4 month of FD vs. WT DN (p<0.05) correlating with an increase in TUNEL positive cells. Higher vascular permeability was observed in ApoE-KO FD, evidenced by the Evans blue leakage and the albumin and α2-M extravasation. At this early stage of the DR, the GFAP expression levels were observed just in astrocytes but not in Müller glial cells (MC) demonstrating non-reactive gliosis in retinas of ApoE-KO FD, which correlated with the GS expression pointing out a normal function of MC. However, a reduction in GFAP immunoreactivity was observed in 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 represent features of human MS, presented vascular dysfunction and neurodegeneration. Thus, this model could offer the opportunity to investigate DR at an early stage, whose prevalence has increased substantially worldwide.