A pro-diabetic diet triggers early functional and structural changes in the rat retina

Abstract

Purpose : Diabetic retinopathy (DR) is the leading cause of blindness in industrial countries before the age of 50 years. The early consequences of diabetes on the retina are nevertheless poorly known. We therefore aimed at characterizing the early effects of a high fructose and high fat diet on the function and structure of the rat retina.

Methods : Male Brown Norway rats (6 weeks of age) were fed for 8 days (n=16), 4 weeks (n=16) and 12 weeks (n=8) with 60% fructose+10% lipid rich diet (HFHF), or a standard chow (n=8). At each time point, intraperitoneal insulin tolerance test (ITT-0.5 U/ml) and intraperitoneal glucose tolerance test (GTT-2g/kg body weight) were carried out. Blood was collected to measure insulin during GTT. Flicker (8Hz), scotopic and photopic single flash electroretinograms (ERG) were recorded from both eyes. At the time of euthanasia, blood was collected to measure glycemia, plasma circulating cytokine levels. Rats were enucleated and the ocular globes were processed for electron microscopy in Epon resin in 86nm-thick sections after counterstaining with uranyl acetate and lead citrate.

Results : At the three time points, HFHF diet increased fasting glycemia (+20% for 8 days, +12% for 4 weeks, +6.5% for 12 weeks) as compared to standard chow diet (p<0.01). Moreover, HFHF feeding induced a significant increase in plasma glucose in ITT (p<0.05) and in GTT (p<0.05), with an elevated insulin response at 12 weeks compared to control group. Our data highlighted a partial loss of cone sensitivity to light in rats fed for 4 weeks with HFHF as revealed by 8Hz Flicker ERG (Δ=0.5 log(I)). However, no significant effect of HFHF was reported on scotopic and photopic single flash ERG. Finally, structural changes were observed, such as deposition of amorphous material between Bruch’s membrane and choriocapillaris in rats fed for 12 weeks with HFHF.

Conclusions : The consumption of high fructose and high fat diet triggered deregulation of glucose metabolism, loss of cone sensitivity and ultrastructural changes in the retina. These findings are consistent with epidemiological data reporting color vision impairment at early stages of diabetes type 2 in human retina, and lipid deposits in Bruch’s membrane at early stages of DR.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.