A common variant in MIR182 is associated with primary open-angle glaucoma in the NEIGHBORHOOD consortium

Purpose : On the contrary to type II diabetes, the consequences of metabolic syndrome (MetS) in the retina are poorly documented. MetS includes insulin resistance, glucose intolerance, dyslipidemia and abdominal adiposity. Vascular changes are strongly associated to metabolic diseases. Thus, we tested the hypothesis that feeding rats with high fructose (60%) and high fat (10%) would contribute to the development of MetS and neovascular retinal complications. Methods : Male Brown Norway rats (6 weeks of age) were fed with a regular chow diet or a 60% rich fructose+10% lipid-rich diet (n=8 in each group) for 4 weeks. At 8 days and 4 weeks, intraperitoneal glucose tolerance test (GTT-2g/kg body weight) and intraperitoneal insulin tolerance test (ITT-0.5U/ml) were performed after a 5 hour-fast. Body fat was quantified using EchoMRI at 4 weeks of diet. Choroidal neovascularization was induced in one eye by laser rupture of Bruch’s membrane (five 532nm-laser burns 300mW, 50 ms, 75 µm). The fate of retinal neovascularization was followed once a week during the following three weeks using fluorescein and indocyanin green angiography. Quantification of the neovascularization was obtained by two independent investigators by assessing the ratio of the fluorescent area to the optical nerve head area using Image J software. Results : High fructose+high fat diet increased fasting glycemia as compared to standard diet group (110±13 vs 98±10mg/dL, p<0.05) at 8 days and 4 weeks. Moreover, fructose feeding during 8 days and 4 weeks induced a significant increase plasma glucose in GTT (+25% at 8 days, +33% at 4 weeks, p<0.05) and ITT (+37% at 8 days, +30% at 4 weeks, p<0.05) compared to control group. After 4 weeks of diet, the data of body composition indicated a 30%-increase of body fat in high fructose+high fat fed rats (p<0.01). Our data highlighted a significant increase of the choroidal vascularization in the rats fed the fructose diet, two (+72%, p<0.05) and three weeks (+67%, p=0.05) after laser induction of neovascularization, compared to rats fed the standard chow diet. Conclusions : Consumption of high fructose and high fat triggered MetS in the rat. At the same time of metabolic consequences, we observed that MetS emphasized choroidal neovascularization in our model. These findings are consistent with epidemiological data reporting MetS as a risk factor for neovascular age-related macular degeneration.