PMID- 37000125
OWN - NLM
STAT- MEDLINE
DCOM- 20230404
LR  - 20230512
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 64
IP  - 3
DP  - 2023 Mar 1
TI  - Lithium Chloride Exerts Anti-Inflammatory and Neuroprotective Effects by 
      Inhibiting Microglial Activation in LPS-Induced Retinal Injury.
PG  - 35
LID - 10.1167/iovs.64.3.35 [doi]
LID - 35
AB  - PURPOSE: To explore the anti-inflammatory and neuroprotective effects of lithium 
      chloride (LiCl) in LPS-induced retinal injury. METHODS: In vitro, primary retinal 
      microglia were pretreated with LiCl and stimulated with lipopolysaccharide (LPS). 
      Pro-inflammatory cytokine production, microglial morphological changes, and 
      inflammation-associated signaling pathways were measured by real-time PCR 
      (RT-PCR), western blotting, and immunofluorescence. Primary retinal neurons were 
      cultured with microglial-derived conditioned medium in the absence or presence of 
      LiCl. Neurotoxicity was evaluated by Cell Counting Kit-8 (CCK-8), terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and 
      gamma-H2AX detection. In vivo, an endotoxin-induced uveitis mice model was 
      established, and each animal was given intraperitoneal injection of LiCl or 
      vehicle. The retinal inflammatory response was measured by hematoxylin and eosin 
      and fluorescent staining, RT-PCR, western blotting, and TUNEL assay. Retinal 
      thickness and function were evaluated by spectral-domain optical coherence 
      tomography and electroretinography. RESULTS: In vitro, LiCl exerted no obvious 
      toxic effects on microglia and significantly decreased proinflammatory factor 
      (inducible nitric oxide synthase, tumor necrosis factor alpha, interleukin 6) 
      production, inhibited microglial activation in morphology, and suppressed nuclear 
      factor kappa B (NF-kappaB), Akt, and phosphatidylinositol 3-kinase (PI3K) 
      phosphorylation. Moreover, LiCl promoted retinal neuron survival and reduced cell 
      apoptosis and the expression of gamma-H2AX. In vivo, LiCl reduced inflammatory 
      infiltrating cells in the vitreous cavity and decreased proinflammatory cytokine 
      expression in retinas. LiCl suppressed LPS-induced microglial activation, 
      proliferation, and migration. Additionally, LiCl reduced LPS-induced apoptosis of 
      ganglion cells and retinal edema and rescued retinal functional damage. 
      CONCLUSIONS: This study demonstrates that LiCl exerts anti-inflammatory and 
      neuroprotective effects by inhibiting microglial activation via the 
      PI3K/Akt/NF-kappaB pathway in LPS-induced retinal injury. LiCl provides a novel and 
      promising option to treat retinal inflammatory diseases.
FAU - Wu, Nandan
AU  - Wu N
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Luo, Qian
AU  - Luo Q
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Huang, Yuke
AU  - Huang Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Wan, Linxi
AU  - Wan L
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Hou, Xiangtao
AU  - Hou X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Jiang, Zihua
AU  - Jiang Z
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Li, Yan
AU  - Li Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Qiu, Jin
AU  - Qiu J
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Chen, Pei
AU  - Chen P
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Yu, Keming
AU  - Yu K
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Zhuang, Jing
AU  - Zhuang J
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of China.
FAU - Yang, Ying
AU  - Yang Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, People's Replubic of 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 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - G4962QA067 (Lithium Chloride)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Lipopolysaccharides/toxicity
MH  - NF-kappa B/metabolism
MH  - Microglia/metabolism
MH  - *Neuroprotective Agents/pharmacology/therapeutic use/metabolism
MH  - Lithium Chloride/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Cell Line
MH  - Anti-Inflammatory Agents/pharmacology
MH  - *Retinal Diseases/pathology
MH  - Cytokines/genetics/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
PMC - PMC10067773
COIS- Disclosure: N. Wu, None; Q. Luo, None; Y. Huang, None; L. Wan, None; X. Hou, 
      None; Z. Jiang, None; Y. Li, None; J. Qiu, None; P. Chen, None; K. Yu, None; J. 
      Zhuang, None; Y. Yang, None
EDAT- 2023/04/01 06:00
MHDA- 2023/04/04 06:42
PMCR- 2023/03/31
CRDT- 2023/03/31 10:33
PHST- 2023/04/04 06:42 [medline]
PHST- 2023/03/31 10:33 [entrez]
PHST- 2023/04/01 06:00 [pubmed]
PHST- 2023/03/31 00:00 [pmc-release]
AID - 2785492 [pii]
AID - IOVS-22-35814 [pii]
AID - 10.1167/iovs.64.3.35 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):35. doi: 10.1167/iovs.64.3.35.