PMID- 35264022
OWN - NLM
STAT- MEDLINE
DCOM- 20220321
LR  - 20220321
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 41
DP  - 2022 Jan-Dec
TI  - Fluorometholone inhibits high glucose-induced cellular senescence in human 
      retinal endothelial cells.
PG  - 9603271221076107
LID - 10.1177/09603271221076107 [doi]
AB  - Diabetic retinopathy (DR) is a common diabetic complication that severely impacts 
      the life quality of diabetic patients. Recently, cellular senescence in human 
      retinal endothelial cells (HRECs) induced by high glucose has been linked to the 
      pathogenesis of DR. Fluorometholone (FML) is a glucocorticoid drug applied in the 
      treatment of inflammatory and allergic disorders of the eye. The objective of the 
      present study is to investigate the protective function of FML on high 
      glucose-induced cellular senescence in HRECs. The in vitro injury model was 
      established by stimulating HRECs with 30 mm glucose. After evaluating the 
      cytotoxicity of FML in HRECs, 0.05% and 0.1% FML were used as the optimal 
      concentration in the entire experiment. It was found that the excessive released 
      inflammatory factors including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 
      (IL-6), and interleukin-8 (IL-8) in HRECs induced by high glucose were 
      significantly suppressed by FML, accompanied by the inhibitory effects on the 
      expression levels of vascular endothelial growth factor (VEGF) and tissue factor 
      (TF). Declined telomerase activity and enhanced senescence-associated 
      beta-galactosidase (SA-beta-gal) activity were found in high glucose-challenged HRECs, 
      which were dramatically alleviated by FML, accompanied by the inactivation of the 
      p53/p21 and retinoblastoma (Rb) signaling. Interestingly, FML ameliorated high 
      glucose-induced dephosphorylation of Akt. Lastly, the protective effects of FML 
      against high glucose-induced cellular senescence in HRECs were abolished by the 
      co-treatment of the PI3K/Akt signaling inhibitor LY294002, suggesting the 
      involvement of this pathway. Taken together, these data revealed that 
      FML-inhibited high glucose-induced cellular senescence mediated by Akt in HERCs, 
      suggesting a novel molecular mechanism of FML.
FAU - Zhou, Xuemei
AU  - Zhou X
AD  - Department of Ophthalmology, Ringgoldid: 117842Weihai Municipal Hospital, Cheeloo 
      College of Medicine, Shandong University, Weihai, China.
FAU - Wang, Lifeng
AU  - Wang L
AD  - Department of Cardiology, Ringgoldid: 194024The Fourth Affiliated Hospital of 
      Harbin Medical University, Harbin, China.
FAU - Zhang, Zhongwei
AU  - Zhang Z
AD  - Department of Ophthalmology, Ringgoldid: 117842Weihai Municipal Hospital, Cheeloo 
      College of Medicine, Shandong University, Weihai, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Ophthalmology, Ringgoldid: 117842Weihai Municipal Hospital, Cheeloo 
      College of Medicine, Shandong University, Weihai, China.
FAU - Qu, Qun
AU  - Qu Q
AD  - Department of Ophthalmology, Ringgoldid: 117842Weihai Municipal Hospital, Cheeloo 
      College of Medicine, Shandong University, Weihai, China.
FAU - Zu, Yuanyuan
AU  - Zu Y
AD  - Department of Ophthalmology, Ringgoldid: 117842Weihai Municipal Hospital, Cheeloo 
      College of Medicine, Shandong University, Weihai, China.
FAU - Shi, Dejing
AU  - Shi D
AD  - Department of Ophthalmology, Ringgoldid: 194024The Fourth Affiliated Hospital of 
      Harbin Medical University, Harbin, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Protective Agents)
RN  - SV0CSG527L (Fluorometholone)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured/drug effects
MH  - Cellular Senescence/*drug effects
MH  - Diabetes Mellitus, Experimental
MH  - Diabetic Retinopathy/physiopathology/*prevention & control
MH  - Endothelial Cells/*drug effects
MH  - Fluorometholone/administration & dosage/*pharmacology
MH  - Humans
MH  - Protective Agents/administration & dosage/*pharmacology
MH  - Retina/*drug effects
OTO - NOTNLM
OT  - Akt
OT  - cell senescence
OT  - diabetic retinopathy
OT  - fluorometholone
OT  - p53
EDAT- 2022/03/11 06:00
MHDA- 2022/03/22 06:00
CRDT- 2022/03/10 05:32
PHST- 2022/03/10 05:32 [entrez]
PHST- 2022/03/11 06:00 [pubmed]
PHST- 2022/03/22 06:00 [medline]
AID - 10.1177/09603271221076107 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221076107. doi: 
      10.1177/09603271221076107.