Biochemical and functional retinal changes in a new experimental mouse model of diabetic retinopathy

PAZ MC; SUBIRADA CALDARONE PAULA; RIDANO MAGALI E; CASTRO C; SANCHEZ MC

Otro; ARVO Annual Meeting; 2016

In this work we propose to characterize a mouse model of DR that involves the SM alterations and mimics the different stages observed in humans.MATERIALS AND METHODSFor this purpose, we used C57BL/6 (WT) and Apolipoprotein E knockout mice (ApoE-KO) either a normal chow (ND) or a 10% w/v fructose (FD) in drinking water from 2 months of age. At 8 months old, lipid and glucose levels in blood were analyzed and retinal function studies (ERG) were performed. Histochemical and immunofluorescence (IF) analysis were performed on retinal tissue.RESULTSAfter the 6 month feeding period, WT FD mice (n= 9) as well as ApoE-KO ND (n=10) and FD (n= 9) showed hyperglycemia and dyslipidemia. At this time, a significant decrease in the ERG b- wave and oscillatory potentials (Ops) amplitudes were observed compared to WT ND mice (p<0.05). WT FD mice had diminished OPs whereas in ApoE-KO ND and FD were absent (p<0.05). This effect was reversed in mice treated with pioglitazone (20 mg / kg). Histochemical studies (flatmounts) showed reduced capillary density in the ApoE-KO ND and FD and the number α-SMA positive of cells was also diminished in both ApoE-KO and WT FD. In addition, TUNEL-positive cells were observed in the ganglion cell layer in WT FD animals, increasing in ApoE-KO ND and FD respect to WT ND mice (p<0.05). The GFAP expression was observed in astrocytes in WT ND, whereas WT FD also showed GFAP expression in activated Müller cells, being increased in both ApoE-KO mice.CONCLUSIONThe results indicate that at 8M, WT FD mice and both groups of ApoE-KO showed retinal changes consistent with DR. Further studies should now be conducted in order to characterize the mechanisms involved in these animal models.