PMID- 36383351
OWN - NLM
STAT- MEDLINE
DCOM- 20221118
LR  - 20221124
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 63
IP  - 12
DP  - 2022 Nov 1
TI  - Type 2 Diabetes Mellitus Makes Corneal Endothelial Cells Vulnerable to 
      Ultraviolet A-Induced Oxidative Damage Via Decreased DJ-1/Nrf2/NQO1 Pathway.
PG  - 25
LID - 10.1167/iovs.63.12.25 [doi]
LID - 25
AB  - PURPOSE: The purpose of this study was to investigate whether type 2 diabetes 
      mellitus (T2DM) makes corneal endothelial cells (CECs) suffer from more severe 
      ultraviolet A (UVA)-induced oxidative damage and explore its mechanisms via 
      measuring the oxidant level and the antioxidant level in vitro. METHODS: Corneas 
      of spontaneous T2DM db/db mice and non-diabetes littermate control mice were 
      irradiated with UVA, leading to oxidative damage of CECs. Anterior 
      segment-optical coherence tomography, corneal image, and CECs 
      immunohistochemistry staining were taken thereafter to measure central corneal 
      thickness, corneal edema degree, and damage extent of CECs. In vitro, human 
      corneal endothelial cells line B4G12 (HCECs) treated with high glucose (HG) and 
      low glucose (LG) were exposed to UVA light separately. Subsequently, cellular 
      proliferation, apoptosis, pro-oxidant factors, such as reactive oxygen species 
      (ROS), antioxidant factors including Parkinson's disease protein 7 (DJ-1), 
      nuclear factor-erythroid 2 related factor 2 (Nrf2), phosphorylated-Nrf2, and 
      NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured. RESULTS: T2DM mice 
      presented greater oxidant damage of CECs and more distinct corneal edema compared 
      with control mice when they were irradiated with the 150 J/cm2 UVA light. In 
      vitro, HCECs in HG condition showed a significant decrease of proliferation, 
      higher apoptosis extent, more ROS generation, lower expressions of 
      DJ-1/Nrf2/NQO1, and distinct reduction of Nrf2 nuclear translocation compared to 
      those in LG condition after exposing to 5 J/cm2 UVA light. CONCLUSIONS: Increase 
      of ROS, downregulation of DJ-1/Nrf2/NQO1 expressions, and decrease of Nrf2 
      nuclear translocation could result in that T2DM makes CECs more vulnerable to 
      oxidative damage.
FAU - Zhang, Xueling
AU  - Zhang X
AD  - Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan 
      University, Shanghai, China.
AD  - Department of Ophthalmology, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese 
      Academy of Medical Sciences, Shanghai, China.
FAU - Qiu, Jini
AU  - Qiu J
AD  - Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan 
      University, Shanghai, China.
AD  - Department of Ophthalmology, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese 
      Academy of Medical Sciences, Shanghai, China.
FAU - Huang, Feifei
AU  - Huang F
AD  - Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan 
      University, Shanghai, China.
AD  - Department of Ophthalmology, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese 
      Academy of Medical Sciences, Shanghai, China.
FAU - Shan, Kun
AU  - Shan K
AD  - Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan 
      University, Shanghai, China.
AD  - Department of Ophthalmology, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese 
      Academy of Medical Sciences, Shanghai, China.
FAU - Zhang, Chaoran
AU  - Zhang C
AD  - Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan 
      University, Shanghai, China.
AD  - Department of Ophthalmology, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese 
      Academy of Medical Sciences, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Antioxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Oxidants)
RN  - EC 1.6.5.2 (NQO1 protein, human)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - NF-E2-Related Factor 2/metabolism
MH  - Antioxidants/pharmacology/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *Diabetes Mellitus, Type 2
MH  - Endothelial Cells/metabolism
MH  - *Corneal Edema
MH  - Oxidative Stress
MH  - Glucose
MH  - Oxidants
MH  - NAD(P)H Dehydrogenase (Quinone)
PMC - PMC9680587
COIS- Disclosure: X. Zhang, None; J. Qiu, None; F. Huang, None; K. Shan, None; C. 
      Zhang, None
EDAT- 2022/11/17 06:00
MHDA- 2022/11/19 06:00
PMCR- 2022/11/16
CRDT- 2022/11/16 11:32
PHST- 2022/11/16 11:32 [entrez]
PHST- 2022/11/17 06:00 [pubmed]
PHST- 2022/11/19 06:00 [medline]
PHST- 2022/11/16 00:00 [pmc-release]
AID - 2783859 [pii]
AID - IOVS-22-35906 [pii]
AID - 10.1167/iovs.63.12.25 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2022 Nov 1;63(12):25. doi: 10.1167/iovs.63.12.25.