α2-Macroglobulin/ LRP-1 system expression in a non-proliferative retinopathy induced by metabolic syndrome in mice

PAZ, MARÍA C.; VAGLIENTI, MARIA V.; BARCELONA, PABLO F.; SÁNCHEZ, MARÍA C.

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022

Metabolic Syndrome (MetSyn) is a complex disorder of metabolismthat affects different organs including the retina, triggering retinopathy.This disease presents, in addition to vascular alterations, aprogressive neuronal degeneration. In this sense, α2-Macroglobulin(α2-M) has been proposed as a mediator of neurotoxicity, throughtheir specific receptor, LRP-1. The purpose of this work was to evaluategene and protein expression of α2-M/ LRP-1 system in retinasof mouse model of MetSyn that exhibits features of early stage(non-proliferative) of retinopathy, such as neuronal impairmentand mild vascular alterations. C57BL/6 (WT) and Apolipoprotein Eknockout (ApoE KO) mice fed with normal diet (ND) or 10% w/vfructose diet (FD) in drinking water from 2 months of age were used.After 3 months of diet, retinal extracts were obtained for Westernblot, qRT-PCR and retinal cryosections for immunofluorescenceanalysis. Data was statistically analyzed by two-way ANOVA andBonferroni post-hoc (p ≤ 0.05). All experimental procedures will becarried out following the standards of The Association for Researchin Vision and Ophthalmology (ARVO) and the ethics committee ofFCQ- UNC. The results showed α2-M mRNA expression in miceretina and a significant increase of α2-M protein expression in retinalextracts of ApoE KO mice with both diets [WT ND vs ApoE KO FD(p< 0,0001) vs ApoE KO FD (p< 0,039)], demonstrating that theirexpression is increased in mice with metabolic alterations. However,LRP-1 protein expression showed no differences between theexperimental groups. Immunofluorescence results showed α2-Mand LRP-1 protein expression, principally in the inner nuclear layerand in the inner limiting membrane of mouse retina. These resultsare more than encouraging and strongly support the study of therole of α2-M/ LRP-1 system in early stage of retinopathy inducedby MetSyn.