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Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and Protracted Microvascular Retinopathy.

Abstract To characterize retinal mitochondrial respiration associated with type 2 diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus Arvicanthis, species niloticus).
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title investigative ophthalmology & visual science
Publication Year Start




PMID- 28763556
OWN - NLM
STAT- In-Process
DA  - 20170801
LR  - 20170801
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 10
DP  - 2017 Aug 01
TI  - Modifications in Retinal Mitochondrial Respiration Precede Type 2 Diabetes and
      Protracted Microvascular Retinopathy.
PG  - 3826-3839
LID - 10.1167/iovs.17-21929 [doi]
AB  - Purpose: To characterize retinal mitochondrial respiration associated with type 2
      diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus
      Arvicanthis, species niloticus). Methods: Nile rats were fed a standard rodent
      diet that resulted in rising glucose levels from 6 months. Age-matched control
      animals were fed a high-fiber diet that prevented diabetes up to 18 months. The
      functional status of specific retinal mitochondrial components and mitochondrial 
      outer membrane integrity were studied by using high-resolution respirometry.
      Ocular complications were documented with funduscopy, electroretinography (ERG), 
      and trypsin digestion of retinal vasculature. Results: Mitochondrial functional
      changes were detected during hyperinsulinemia with maintained normoglycemia (2
      months), corresponding to stage 1 of human T2D. Our data showed increased
      contribution of mitochondrial respiration through the NADH pathway relative to
      maximal oxidative phosphorylation capacity, with simultaneous electron entry into
      NADH (Complex I and related dehydrogenases) and succinate (Complex II) pathways. 
      These compensatory events coincided with compromised mitochondrial outer membrane
      integrity. The first clinical sign of retinopathy (pericyte loss) was only
      detected at 12 months (after 6 months of sustained hyperglycemia) alongside a
      common ocular complication of diabetes, cataractogenesis. Further prolongation of
      hyperglycemia (from 12 to 18 months) led to capillary degeneration and delayed
      photopic ERG oscillatory potentials. Conclusions: Oxidative phosphorylation
      compensatory changes in the retina can be detected as early as 2 months, before
      development of hyperglycemia, and are associated with reduced mitochondrial outer
      membrane integrity.
FAU - Han, Woo Hyun
AU  - Han WH
AD  - Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton,
      Alberta, Canada.
FAU - Gotzmann, Jonathan
AU  - Gotzmann J
AD  - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
FAU - Kuny, Sharee
AU  - Kuny S
AD  - Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton,
      Alberta, Canada.
FAU - Huang, Hui
AU  - Huang H
AD  - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
FAU - Chan, Catherine B
AU  - Chan CB
AD  - Department of Physiology, University of Alberta, Edmonton, Alberta, Canada
      3Agriculture, Food and Nutritional Science, University of Alberta, Edmonton,
      Alberta, Canada.
FAU - Lemieux, Helene
AU  - Lemieux H
AD  - Faculty Saint-Jean, University of Alberta, Edmonton, Alberta, Canada.
FAU - Sauve, Yves
AU  - Sauve Y
AD  - Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton,
      Alberta, Canada 2Department of Physiology, University of Alberta, Edmonton,
      Alberta, Canada.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
EDAT- 2017/08/02 06:00
MHDA- 2017/08/02 06:00
CRDT- 2017/08/02 06:00
AID - 2646831 [pii]
AID - 10.1167/iovs.17-21929 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):3826-3839. doi:
      10.1167/iovs.17-21929.