PMID- 29376145
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2473-5477 (Print)
IS  - 2473-5477 (Electronic)
IS  - 2473-5477 (Linking)
VI  - 4
IP  - 4
DP  - 2017
TI  - The Role of Txnip in Mitophagy Dysregulation and Inflammasome Activation in 
      Diabetic Retinopathy: A New Perspective.
LID - 555643 [pii]
LID - 10.19080/jojo.2017.04.555643 [doi]
AB  - Mitochondria are responsible for bioenergetics, metabolism and apoptosis signals 
      in health and disease. The retina being a part of the central nervous system 
      consumes large amounts of glucose and oxygen to generate ATP via the 
      mitochondrial oxidative phosphorylation for its phototransduction and visual 
      function. During ATP generation, electrons leak from the mitochondrial electron 
      transport chain, which is captured by molecular oxygen to produce reactive oxygen 
      species (ROS). These mtROS damage mitochondrial proteins, mtDNA, and membrane 
      lipids and release them in the cytosol. Mitochondrial components are recognized 
      as danger-associated molecular patterns (DAMPS) by cytosolic pattern recognition 
      receptors such as NOD-like receptors, NLRP3 inflammasomes. They process 
      pro-caspase-1 to active caspase-1, which cleaves pro-inflammatory IL-1beta o mature 
      IL-1beta causing inflammation and cell death by pyroptosis. To counter the damaging 
      action of mtROS and inflammasomes in fully differentiated cells in the retina, 
      the removal of the damaged and dysfunctional mitochondria by a double-membrane 
      autophagic process via lysosomal degradation called mitophagy is critical for 
      mitochondrial homeostasis and cell survival. Nonetheless, under chronic diseases 
      including diabetic retinopathy (DR), mitophagy dysregulation and NLRP3 
      inflammasome activation exist, which cause premature cell death and disease 
      progression. Recently, the thioredoxin-interacting protein TXNIP, which is 
      strongly induced by diabetes and inhibits anti-oxidant function of thioredoxin, 
      has been implicated in mitochondrial dysfunction, mitophagic dysregulation and 
      NLRP3 inflammasome activation in DR. Therefore, TXNIP silencing or 
      pharmacological inhibition may normalize mitophagic flux and NLRP3 inflammasome 
      activation, which will prevent or slow down the progression of DR.
FAU - Singh, Lalit P
AU  - Singh LP
AD  - Department of Anatomy and Cell Biology, Wayne State University School of 
      Medicine, USA.
AD  - Department of Ophthalmology, Wayne State University School of Medicine, USA.
FAU - Devi, Takhellambam S
AU  - Devi TS
AD  - Department of Anatomy and Cell Biology, Wayne State University School of 
      Medicine, USA.
FAU - Yumnamcha, Thangal
AU  - Yumnamcha T
AD  - Department of Anatomy and Cell Biology, Wayne State University School of 
      Medicine, USA.
LA  - eng
GR  - P30 EY004068/EY/NEI NIH HHS/United States
GR  - R01 EY023992/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20170915
PL  - United States
TA  - JOJ Ophthalmol
JT  - JOJ ophthalmology
JID - 101713317
PMC - PMC5786434
MID - NIHMS907209
OTO - NOTNLM
OT  - Diabetic retinopathy
OT  - Mitophagy
OT  - NLRP3 inflammasome
OT  - TXNIP
OT  - mt-Keima
EDAT- 2018/01/30 06:00
MHDA- 2018/01/30 06:01
PMCR- 2018/01/26
CRDT- 2018/01/30 06:00
PHST- 2018/01/30 06:00 [entrez]
PHST- 2018/01/30 06:00 [pubmed]
PHST- 2018/01/30 06:01 [medline]
PHST- 2018/01/26 00:00 [pmc-release]
AID - 555643 [pii]
AID - 10.19080/jojo.2017.04.555643 [doi]
PST - ppublish
SO  - JOJ Ophthalmol. 2017;4(4):10.19080/jojo.2017.04.555643. doi: 
      10.19080/jojo.2017.04.555643. Epub 2017 Sep 15.