April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Hyperlipedemia Exacerbates Diabetic Retinopathy Via Nf-B Activation
Author Affiliations & Notes
  • Shintaro Nakao
    Ophthalmology, Kyushu University, Fukuoka, Japan
    Ophthalmology, Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Souska Zandi
    Ophthalmology, Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
    Department of Radiology, Harvard Medical School, The Center for Excellence in Functional and Molecular Imaging, Brigham and Women’s Hospital, Boston, Massachusetts
  • Dawei Sun
    Ophthalmology, Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
  • Tatsuro Ishibashi
    Ophthalmology, Kyushu University, Fukuoka, Japan
  • K.C. Hayes
    Department of Biology, Foster Biomedical Research Laboratory, Brandeis University, Waltham, Massachusetts
  • Ali Hafezi-Moghadam
    Ophthalmology, Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts
    Department of Radiology, Harvard Medical School, The Center for Excellence in Functional and Molecular Imaging, Brigham and Women’s Hospital, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Shintaro Nakao, None; Souska Zandi, None; Dawei Sun, None; Tatsuro Ishibashi, None; K.C. Hayes, None; Ali Hafezi-Moghadam, None
  • Footnotes
    Support  NIH grant AI050775, MPOB, and American Health Assistance Foundation.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3586. doi:
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      Shintaro Nakao, Souska Zandi, Dawei Sun, Tatsuro Ishibashi, K.C. Hayes, Ali Hafezi-Moghadam; Hyperlipedemia Exacerbates Diabetic Retinopathy Via Nf-B Activation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3586.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 
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