Metabolic Syndrome Triggered by Fructose Diet Impairs Neuronal Function and Vascular Integrity in ApoE-KO Mouse Retinas: Implications of Autophagy Deficient Activation

PAZ, MARÍA C.; BARCELONA, PABLO F.; SUBIRADA, PAULA V.; RIDANO, MAGALI E.; CHIABRANDO, GUSTAVO A.; CASTRO, CLAUDIA; SÁNCHEZ, MARÍA C.

Frontiers in Cell and Developmental Biology

Frontiers Editorial Office

Año: 2020 vol. 8

Metabolic syndrome is a disorder characterized by a constellation of clinical findingssuch as elevated blood glucose, hyperinsulinemia, dyslipidemia, hypertension, andobesity. A positive correlation has been found between metabolic syndrome or itscomponents and retinopathy, mainly at microvascular level, in patients without a historyof diabetes. Here, we extend the investigations beyond the vascular componentanalyzing functional changes as well as neuronal and glial response in retinas ofApolipoprotein E knockout (ApoE-KO) mice fed with 10% w/v fructose diet. Giventhat autophagy dysfunction is implicated in retinal diseases related to hyperglycemiaand dyslipidemia, the activation of this pathway was also analyzed. Two months offructose intake triggered metabolic derangements in ApoE-KO mice characterized bydyslipidemia, hyperglycemia and hyperinsulinemia. An increased number of TUNELpositive cells, in addition to the ganglion cell layer, was observed in the inner nuclearlayer in retina. Vascular permeability, evidenced by albumin?Evans blue leakage andextravasation of albumin was also detected. Furthermore, a significant decrease of theglial fibrillary acidic protein expression was confirmed by Western blot analysis. Absenceof both Müller cell gliosis and pro-angiogenic response was also demonstrated. Finally,retinas of ApoE-KO FD mice showed defective autophagy activation as judged by LC3BmRNA and p62 protein levels correlating with the increased cell death. These resultsdemonstrated that FD induced in ApoE-KO mice biochemical alterations compatiblewith metabolic syndrome associated with neuronal impairment and mild vascularalterations in the retina.