a2-MACROGLOBULIN/ LRP-1 SYSTEM EXPRESSION IN A NON-PROLIFERATIVE RETINOPATHY INDUCED BY METABOLIC SYNDROME IN MICE

PAZ, M. C; SANCHEZ, MC; BARCELONA, P; VAGLIENTI, MV

Mar del Plata

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2022

Sociedad Argentina de Investigación Clínica (SAIC)

Metabolic Syndrome (MetSyn) is a complex disorder of metabolism that affects different organs including the retina, triggering retinopathy. This disease presents, in addition to vascular alterations, a progressive neuronal degeneration. In this sense, α2-Macroglobulin (α2-M) has been proposed as a mediator of neurotoxicity, through their specific receptor, LRP-1. The purpose of this work was to evaluate gene and protein expression of α2-M/ LRP-1 system in retinas of mouse model of MetSyn that exhibits features of early stage (non-proliferative) of retinopathy, such as neuronal impairment and mild vascular alterations. C57BL/6 (WT) and Apolipoprotein E knockout (ApoE KO) mice fed with normal diet (ND) or 10% w/v fructose diet (FD) in drinking water from 2 months of age were used. After 3 months of diet, retinal extracts were obtained for Western blot, qRT-PCR and retinal cryosections for immunofluorescence analysis. Data was statistically analyzed by two-way ANOVA and Bonferroni post-hoc (p ≤ 0.05). All experimental procedures will be carried out following the standards of The Association for Research in Vision and Ophthalmology (ARVO) and the ethics committee of FCQ- UNC. The results showed α2-M mRNA expression in mice retina and a significant increase of α2-M protein expression in retinal extracts 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 their expression is increased in mice with metabolic alterations. However, LRP-1 protein expression showed no differences between the experimental groups. Immunofluorescence results showed α2-M and LRP-1 protein expression, principally in the inner nuclear layer and in the inner limiting membrane of mouse retina. These results are more than encouraging and strongly support the study of the role of α2-M/ LRP-1 system in early stage of retinopathy induced by MetSyn.