PMID- 31737079
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1687-966X (Print)
IS  - 1687-9678 (Electronic)
VI  - 2019
DP  - 2019
TI  - Human Umbilical Cord Mesenchymal Stem Cells Attenuate Ocular Hypertension-Induced 
      Retinal Neuroinflammation via Toll-Like Receptor 4 Pathway.
PG  - 9274585
LID - 10.1155/2019/9274585 [doi]
LID - 9274585
AB  - Glaucoma is characterized by progressive, irreversible damage to the retinal 
      ganglion cells (RGCs) and their axons. Our previous study has shown that the 
      intravitreal transplantation of human umbilical cord mesenchymal stem cells 
      (hUC-MSCs) reveals a neuroprotective role in microsphere injection-induced ocular 
      hypertension (OHT) rat models. The protection is related to the modulation of 
      glial cells, but the mechanisms are still unknown. The purpose of the present 
      study is to clarify the potential neuroinflammatory mechanisms involved in the 
      neuroprotective role of hUC-MSCs. OHT models were established with SD rats 
      through intracameral injection of polystyrene microbeads. The animals were 
      randomly divided into three groups: the normal group, the OHT+phosphate-buffered 
      saline (PBS) group, and the OHT+hUC-MSC group. Retinal morphology was evaluated 
      by measuring the inner retinal thickness via optical coherence tomography (OCT). 
      Retinal cell apoptosis was examined by TUNEL staining and Bax expression 14 days 
      following hUC-MSC transplantation. The expression levels of glial fibrillary 
      acidic protein (GFAP), ionized calcium binding adapter molecule 1 (iba-1), and 
      toll-like receptor 4 (TLR4) were assessed via immunohistochemistry, real-time 
      quantitative PCR, and Western blot. RNA and proteins were extracted 14 days 
      following transplantation, and the expression levels of the TLR4 signaling 
      pathways and proinflammatory cytokines-myeloid differentiation factor 88 (MyD88), 
      IL-1beta, IL-6, and TNF-alpha-were determined. OCT showed that the intravitreal 
      transplantation of hUC-MSCs significantly increased the inner thickness of the 
      retina. A TUNEL assay and the expression of Bax suggested that the apoptosis of 
      retinal cells was decreased by hUC-MSCs 14 days following transplantation. 
      Intravitreal hUC-MSC transplantation resulted in a decreased expression of GFAP, 
      iba-1, TLR4, MyD88, IL-1beta, IL-6, and TNF-alpha 14 days following transplantation. In 
      addition, via in vitro experiments, we found that the increased expression of the 
      TLR4 signaling pathway induced by lipopolysaccharide (LPS) was markedly decreased 
      after hUC-MSCs were cocultured with rMC-1 and BV2 cells. These findings indicate 
      that hUC-MSC transplantation attenuates OHT-induced retinal neuroinflammation via 
      the TLR4 pathway.
CI  - Copyright (c) 2019 Shangli Ji et al.
FAU - Ji, Shangli
AU  - Ji S
AUID- ORCID: 0000-0003-1984-2008
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.
AD  - Aier Eye Institute, Changsha, Hunan, China.
FAU - Xiao, Jie
AU  - Xiao J
AD  - Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South 
      University, Changsha, Hunan, China.
FAU - Liu, Jian
AU  - Liu J
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.
AD  - Aier Eye Institute, Changsha, Hunan, China.
FAU - Tang, Shibo
AU  - Tang S
AUID- ORCID: 0000-0003-2737-6780
AD  - Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.
AD  - Aier Eye Institute, Changsha, Hunan, China.
LA  - eng
PT  - Journal Article
DEP - 20191015
PL  - United States
TA  - Stem Cells Int
JT  - Stem cells international
JID - 101535822
PMC - PMC6815608
COIS- No conflicting interests exist for any of the authors.
EDAT- 2019/11/19 06:00
MHDA- 2019/11/19 06:01
PMCR- 2019/10/15
CRDT- 2019/11/19 06:00
PHST- 2019/05/17 00:00 [received]
PHST- 2019/07/30 00:00 [revised]
PHST- 2019/08/07 00:00 [accepted]
PHST- 2019/11/19 06:00 [entrez]
PHST- 2019/11/19 06:00 [pubmed]
PHST- 2019/11/19 06:01 [medline]
PHST- 2019/10/15 00:00 [pmc-release]
AID - 10.1155/2019/9274585 [doi]
PST - epublish
SO  - Stem Cells Int. 2019 Oct 15;2019:9274585. doi: 10.1155/2019/9274585. eCollection 
      2019.