PMID- 37937143
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231109
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 10
DP  - 2023
TI  - Resveratrol regulates macrophage recruitment and M1 macrophage polarization and 
      prevents corneal allograft rejection in rats.
PG  - 1250914
LID - 10.3389/fmed.2023.1250914 [doi]
LID - 1250914
AB  - INTRODUCTION: Resveratrol is an immune modulator that can reduce M1 macrophage 
      polarization in vitro. Reducing macrophage recruitment and M1 polarization can 
      prevent corneal allograft rejection (CGR). In this study, rat corneal allograft 
      rejection models were established to explore the effects of resveratrol on CGR 
      and macrophages and the underlying mechanisms after corneal transplantation. 
      METHODS: Corneal allograft models were established, and 100 mg/kg resveratrol was 
      injected intraperitoneally. The corneal allografts were assessed clinically using 
      the Holland rejection scoring system, anterior segment photography, and anterior 
      segment optical coherence tomography. Corneal macrophages, pro-inflammatory 
      cytokines, and corneal lymphatic vessels were detected using hematoxylin and 
      eosin staining, immunofluorescence staining, and real-time quantitative 
      polymerase chain reaction (qRT-PCR). Dendritic cells (DCs) in cervical lymph 
      nodes were explored using flow cytometry. RNA sequencing experiments were 
      conducted to identify the mechanisms through which resveratrol affected CGR. The 
      results were verified using Simple Western analysis. Pro-inflammatory cytokines 
      by macrophages in vitro were measured using qRT-PCR and enzyme-linked 
      immunosorbent assays. RESULTS: Resveratrol significantly prolonged the survival 
      of corneal grafts and reduced graft edema and central corneal thickness. Corneal 
      macrophage recruitment and M1 macrophage polarization decreased significantly 
      after corneal transplantation in the resveratrol group. Resveratrol also reduced 
      pro-inflammatory cytokines in corneal grafts and suppressed the early generation 
      of cornea lymphatic vessels and the recruitment of cornea inflammatory cells 
      14 days after surgery. Resveratrol decreased the proportion of DCs in ipsilateral 
      cervical lymph nodes. The effect of resveratrol on CGR was related to the 
      phosphatidylinositol 3-kinase/protein kinase-B (PI3K/Akt) pathway. Resveratrol 
      reduced the secretion of pro-inflammatory cytokines by M1 macrophages in vitro. 
      CONCLUSION: Our findings suggest that resveratrol can reduce corneal macrophage 
      recruitment and M1 macrophage polarization after corneal transplantation in rats 
      and prevent CGR. The PI3K/Akt pathway may be an important mechanism that warrants 
      further research.
CI  - Copyright (c) 2023 Xu, Guo, Hou, Ma, Dong, Ouyang, Wu and Huang.
FAU - Xu, Chenjia
AU  - Xu C
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Guo, Ruilin
AU  - Guo R
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Hou, Chao
AU  - Hou C
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Ma, Minglu
AU  - Ma M
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Dong, Xiaojuan
AU  - Dong X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Ouyang, Chen
AU  - Ouyang C
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Wu, Jing
AU  - Wu J
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
FAU - Huang, Ting
AU  - Huang T
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual 
      Science, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20231023
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC10626464
OTO - NOTNLM
OT  - PI3K/Akt pathway
OT  - corneal transplantation
OT  - immune rejection
OT  - macrophages
OT  - resveratrol
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/11/08 06:42
MHDA- 2023/11/08 06:43
PMCR- 2023/10/23
CRDT- 2023/11/08 04:02
PHST- 2023/06/30 00:00 [received]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/11/08 06:43 [medline]
PHST- 2023/11/08 06:42 [pubmed]
PHST- 2023/11/08 04:02 [entrez]
PHST- 2023/10/23 00:00 [pmc-release]
AID - 10.3389/fmed.2023.1250914 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2023 Oct 23;10:1250914. doi: 10.3389/fmed.2023.1250914. 
      eCollection 2023.