Hyperlipedemia Exacerbates Diabetic Retinopathy Via Nf-B Activation

Abstract

Purpose: : Dietary patterns are shifting from plant-based to animal-based proteins and fats with urbanization of the developing countries. The resulting metabolic changes significantly increase morbidity, for instance in diabetic retinopathy (DR), an inflammatory and microvascular complication of diabetes. This work elucidates on a molecular level the impact of diet-induced hypelipidemia on diabetic microvascular injury.

Methods: : Diabetic animals by STZ were fed normal chow or various high fat diets (high polyunsaturated vs high saturated fat with or without cholesterol). Custom-designed molecular imaging probes, αICAM-1 mAb- or IgG-conjugated fluorescent microspheres (MS), were injected to perform in vivo studies of retinal vessels. Retinal leukocyte accumulation and endothelial damage were examined with Con A and PI staining, respectively. NF-ΚB activation and endothelial ICAM-1 in retina were examined with western blotting and in vivo molecular imaging.

Results: : Retinal leukocyte accumulation and endothelial damage were significantly higher in diabetic animals fed normal chow (n=7&9, 43.6±4.6 vs 24.8±4.6, P=0.006, 3.8±0.6 vs 14.5±1.5, P=0.03, respectively). High fat diet significantly enhanced leukocyte adhesion and endothelial damage in diabetic retinas compared with chow diet-fed animals (n=7&9, 99.9±7.5, P<0.00001, 42.6±4.0, P<0.05). Diabetic animals on high fat diet showed significantly higher NF-ΚB activation compared with normally fed diabetic controls. Our in vivo molecular imaging revealed higher ICAM-1 levels in diabetic animals on high fat diet compared to diabetic controls on normal chow. High saturated fat with cholesterol caused highest increase in leukocyte adhesion (49.4±6.4 vs 106.7±20.3, P=0.03) and endothelial damage (10.9±2.3 vs 19.7±1.8, P=0.04) in DR (n=12).

Conclusions: : Dietary lipids accelerate diabetic retinal inflammation and vascular damage via endothelial NF-ΚB-signaling. This work reveals a synergistic effect of blood lipids and glucose in causing retinal inflammation and endothelial injury. Our in vivo molecular imaging of the retinal endothelium is a powerful research tool for elucidating the complex dynamics in DR. This approach can be further developed for use in patients for early diagnosis of DR.

Keywords: diabetic retinopathy • lipids • imaging/image analysis: non-clinical