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Maria Constanza Paz, Paula Subirada, Magali Ridano, Claudia Castro, Maria Cecilia Sanchez; Biochemical and functional retinal changes in a new experimental mouse model of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5442.
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© ARVO (1962-2015); The Authors (2016-present)
Type 2 diabetes mellitus (T2DM), which is a metabolic syndrome (MS), triggers micro vascular complications in the retina know as diabetic retinopathy (DR). Several animal models of DR have been very useful; however, none of these have been able to reproduce completely anatomic and functional abnormalities of this pathology.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.
For 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.
After 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.
The 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.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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