PMID- 35345831
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220405
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Pharmacological Inhibition of Glutaminase 1 Attenuates Alkali-Induced Corneal 
      Neovascularization by Modulating Macrophages.
PG  - 1106313
LID - 10.1155/2022/1106313 [doi]
LID - 1106313
AB  - Corneal neovascularization (CoNV) in response to chemical burns is a leading 
      cause of vision impairment. Although glutamine metabolism plays a crucial role in 
      macrophage polarization, its regulatory effect on macrophages involved in 
      chemical burn-induced corneal injury is not known. Here, we elucidated the 
      connection between the reprogramming of glutamine metabolism in macrophages and 
      the development of alkali burn-induced CoNV. Glutaminase 1 (GLS1) expression was 
      upregulated in the mouse corneas damaged with alkali burns and was primarily 
      located in F4/80-positive macrophages. Treatment with a selective oral GLS1 
      inhibitor, CB-839 (telaglenastat), significantly decreased the distribution of 
      polarized M2 macrophages in the alkali-injured corneas and suppressed the 
      development of CoNV. In vitro studies further demonstrated that glutamine 
      deprivation or CB-839 treatment inhibited the proliferation, adhesion, and M2 
      polarization of bone marrow-derived macrophages (BMDMs) from C57BL/6J mice. 
      CB-839 treatment markedly attenuated the secretion of proangiogenic factors, 
      including vascular endothelial growth factor-A (VEGF-A) and platelet-derived 
      growth factor-BB (PDGF-BB) from interleukin-4- (IL-4-) regulated M2 macrophages. 
      Our findings revealed that GLS1 inhibition or glutamine deprivation prevented 
      alkali-induced CoNV by inhibiting the infiltration and M2 polarization of 
      macrophages. This work suggests that pharmacological GLS1 inhibition is a 
      feasible and effective treatment strategy for chemical burn-related CoNV in 
      humans.
CI  - Copyright (c) 2022 Yifan Feng et al.
FAU - Feng, Yifan
AU  - Feng Y
AUID- ORCID: 0000-0001-8305-1695
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Yang, Xi
AU  - Yang X
AUID- ORCID: 0000-0002-5780-7142
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Huang, Jinhai
AU  - Huang J
AUID- ORCID: 0000-0001-9952-3175
AD  - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan 
      University, Shanghai, China.
AD  - NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, 
      Chinese Academy of Medical Sciences, Shanghai, China.
FAU - Shen, Minqian
AU  - Shen M
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Wang, Liyang
AU  - Wang L
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Chen, Xiuping
AU  - Chen X
AUID- ORCID: 0000-0001-7542-5749
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Yuan, Yuanzhi
AU  - Yuan Y
AUID- ORCID: 0000-0002-5240-3915
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Dong, Chunqiong
AU  - Dong C
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Ma, Xiaoping
AU  - Ma X
AUID- ORCID: 0000-0002-5805-9481
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
FAU - Yuan, Fei
AU  - Yuan F
AUID- ORCID: 0000-0001-6230-9634
AD  - Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20220319
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Alkalies)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 3.5.1.2 (Glutaminase)
SB  - IM
MH  - Alkalies/toxicity
MH  - Animals
MH  - *Corneal Neovascularization/chemically induced/drug therapy
MH  - Glutaminase/adverse effects
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Vascular Endothelial Growth Factor A/pharmacology
PMC - PMC8957416
COIS- The authors declare no conflict of interest.
EDAT- 2022/03/30 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/03/19
CRDT- 2022/03/29 05:15
PHST- 2022/02/02 00:00 [received]
PHST- 2022/02/24 00:00 [accepted]
PHST- 2022/03/29 05:15 [entrez]
PHST- 2022/03/30 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2022/03/19 00:00 [pmc-release]
AID - 10.1155/2022/1106313 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Mar 19;2022:1106313. doi: 10.1155/2022/1106313. 
      eCollection 2022.