September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Exercise inhibits progression of diabetic retinopathy by reducing inflammatory, oxidative stress, and ER stress gene expression in the retina of db/db mice
Author Affiliations & Notes
  • Jing Z Cui
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Matthew Wong
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Aikun Wang
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Ismail Laher
    Anesthesiology, Pharmacology & Therapeutics, Faculty of Medicine , University of British Columbia, Vancouver, British Columbia, Canada
  • Joanne A Matsubara
    Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  • Footnotes
    Commercial Relationships   Jing Cui, None; Matthew Wong, None; Aikun Wang, None; Ismail Laher, None; Joanne Matsubara, None
  • Footnotes
    Support  CIHR MOP 126195
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5434. doi:
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      Jing Z Cui, Matthew Wong, Aikun Wang, Ismail Laher, Joanne A Matsubara; Exercise inhibits progression of diabetic retinopathy by reducing inflammatory, oxidative stress, and ER stress gene expression in the retina of db/db mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5434.

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

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Abstract

Purpose : Current treatments for diabetic retinopathy (DR) are aimed towards proliferative DR (PDR), the end stage of DR. In the early stages of DR, inflammation, oxidative stress, and ER stress all contribute to the progression of DR from non-proliferative DR (NPDR) to PDR. The purpose of this study is to investigate how exercise affects early stages of DR via inflammatory, oxidative stress, and ER stress pathways in a spontaneous type 2 diabetic (db/db) mouse model.

Methods : 5-week old BKS.Cg-m+/+ Lepr db/+/J wild type (WT) and db/db mice were divided and randomly placed into sedentary (Ex-) and exercise (Ex+) groups (n = 7 per group). Over a 7-week period, WT or db/db mice in the Ex+ group were placed on a motorized exercise wheel for 1 hour for 5 days per week at 5.2m/min, while Ex- mice were placed in a non-rotating wheel. Mice were sacrificed at 12 weeks of age and eyes were enucleated and processed for total RNA extraction. Total RNA was purified vitreous, retina, and choroid tissue and expression level was assessed using quantitative PCR (qPCR). Each Ex+ group was compared to their corresponding Ex- group. Results were expressed in mRNA fold change normalized to the housekeeping gene, GADPH, using the 2-ΔΔCt method and values were statistically analyzed. VEGF, HO-1 and TXN1, and GRP78 and CHOP were used to measure levels of inflammation, oxidative stress, and ER stress respectively.

Results : Db/db mice placed in the Ex+ group had reduced expression of VEGF, HO-1, TXN1, and GRP78 compared to those in the Ex- group (Mean fold changes of -7.14, -2.78, -1.92 and -3.57, respectively, p <0.01). There was a trend towards downregulation in the ER stress gene, CHOP, in the Ex+ group when compared to the Ex- group in db/db mice (-1.37, p = 0.073). In WT mice, gene expression in the Ex+ group was reduced for GRP78 (-1.27, p<0.05), but no changes observed for VEGF, HO-1, TXN1, and CHOP (p>0.05).

Conclusions : Evidence suggests levels of mRNA for VEGF, HO-1, TXN1, GRP78, and CHOP parallel with levels of inflammation, oxidative stress and ER stress. Therefore, reduced expression of these genes may indicate that exercise aids in reducing inflammation, oxidative stress, and ER stress in the retina of db/db mice. Future experiments are needed to determine further if exercise may be effective in suppressing early retinal changes associated with DR.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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