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Ali Hafezi-Moghadam, Aliaa Barakat, Shintaro Nakao, Souska Zandi, Dawei Sun, KC Hayes; Western diet-enhanced diabetic retinopathy is not lipid mediated. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3565. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
A high proportion of dietary lipids and especially saturated fats has been regarded deleterious in the development of macrovascular diabetes complications. However, the details of how dietary lipids may contribute to microvascular diabetic complication in the eye are not understood. This study examines, if diets that contain high levels of saturated or polyunsaturated, with or without cholesterol, differentially impact experimental diabetic retinopathy in rats.
Type 1 diabetes was induced in Long-Evans rats (180–200 g, 6–7-wk-old) through intravenous injection of streptozotocin (STZ, 60 mg/kg). Control animals were injected with citrate buffer. We generated purified diets that were high in polyunsaturated fats, high in saturated fats, with or without added cholesterol (1%). Blood glucose (BG), hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), adiponectin, and VEGF-A were measured in all animals.The in vivo expressions of retinal ICAM-1 and VCAM-1 was quantified using our light-based molecular imaging. Custom-designed nano-probes for imaging were generated as described in our previous work. Endothelial injury and leukocyte adhesion to the retinal vessels were quantified in histological flatmounts.
Western diet (WD) significantly increased retinal leukocyte accumulation and endothelial death in diabetic rats. Molecular imaging revealed higher expressions of the endothelial adhesion molecule expressions, ICAM-1 and VCAM-1 in diabetic animals on WD compared to normal. Suppression of endothelial NFkb signaling reduced the WD-induced increase in leukocyte accumulation.Neither high levels of polyunsaturated nor saturated fats increased retinal leukocyte accumulation or endothelial injury. Only diabetic animals on excessive levels of added cholesterol in their purified diets, levels that are far beyond the cholesterol found in a human diet high is saturated fats and cholesterol, showed more leukocyte accumulation compared to the diabetic animals on regular chow.
These results suggest that a high dietary lipid component per se does not exacerbate diabetic retinopathy. Future examination will address the contribution of carbohydrates as another macronutrient that is high in WD as a potential contributor to diabetic retinopathy pathology.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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