April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Long-term Intermittent Fasting (IF) Protects db/db Mice from Development of Diabetic Retinopathy (DR)
Author Affiliations & Notes
  • Maria Grant
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
    Pharmacology and Therapeutics, University of Florida, Gainesville, FL
  • Yuanqing Yan
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Tatiana Salazar
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Ashay D Bhatwadekar
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • James M Dominguez
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Dung Nguyen
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Rui Gao
    Pediactrics, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Elei Beli
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Julia V Busik
    Physiology, Michigan State University, East Lansing, MI
  • Michael E Boulton
    Ophthalmology, Indiana University Perdue University Indianapolis, Indianapolis, IN
  • Footnotes
    Commercial Relationships Maria Grant, None; Yuanqing Yan, None; Tatiana Salazar, None; Ashay Bhatwadekar, None; James Dominguez, None; Dung Nguyen, None; Rui Gao, None; Elei Beli, None; Julia Busik, None; Michael Boulton, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5992. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Maria Grant, Yuanqing Yan, Tatiana Salazar, Ashay D Bhatwadekar, James M Dominguez, Dung Nguyen, Rui Gao, Elei Beli, Julia V Busik, Michael E Boulton; Long-term Intermittent Fasting (IF) Protects db/db Mice from Development of Diabetic Retinopathy (DR). Invest. Ophthalmol. Vis. Sci. 2014;55(13):5992. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: Feeding is a strong circadian entrainer and continuous feeding disrupts normal circadian patterns. Disruption of the circadian clock contributes to disease pathogenesis including diabetes. Using a rat model of type 2 diabetes (T2D) we showed that loss of circadian release of vascular reparative cells is due to bone marrow (BM) neuropathy and precedes development of DR. In this study, we examined the impact of IF on DR in a model of T2D, db/db mice.

Methods: To ascertain whether IF could correct DR and circadian disruption, db/db mice underwent IF for 6 months (mice were fasted 24hr and fed for 24hr; food was removed 5~30min before lights were turned off; beginning of the active phase). Bones were harvested to assess denervation using neurofilament 200 nerve fiber immunohistochemistry. Acelluar capillaries were counted in retinas to assess DR. Bmal1 and Per2 gene expression was tested in suprachiasmatic nucleus (SCN; central clock), liver and BM lineage-sca1+ cells (peripheral clocks). cDNA microarray was performed from liver and cytokines levels were measured in BM supernatant.

Results: T2D (11 months) exhibited DR (as demonstrated by a 2.37 fold increase in number of acellular capillaries), displayed neuropathy, disrupted circadian pattern of hematopoietic stem cells (HSCs) release from the BM, defective migration of HSC to SDF-1, and altered expression of clock genes in retina, HSCs and in the liver compared to controls. IF slightly reduced food intake (12% in db/m and 20% in db/db) and body weight, but there was no change in glycated hemoglobin. db/db mice on IF showed increased survival rate (95.13% survival compared to 83.08% db/db ad lib mice); prevention of DR (30.3 % decrease in acellular capillaries compared to db/db ad lib mice; p<0.05%), and absence of BM neuropathy (22.36±8.21 NF200+ fiber/field compared to 11.78±7.18 db/db ad lib; p<0.05). IF restored the altered circadian pattern of HSCs release from BM, HSCs migration capability in vitro and circadian clock gene expression to normal levels. IF increased liver eNOS expression and increased expression of key genes associated with reducing inflammation (Anxa1), enhancing insulin sensitivity (Lcn13) and lipid metabolism (Plac8).

Conclusions: The protective effects of IF support the notion that IF prevents circadian dysfunction and development of DR in db/db mice.

Keywords: 458 circadian rhythms • 499 diabetic retinopathy • 721 stem cells  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×