April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Improvement of Radiotherapy-induced lacrimal gland injury by IPS cell-derived conditioned medium via inhibition of P38/JNK pathway and cylindromatosis -dependent regulation
Author Affiliations & Notes
  • Yanqing Zhang
    Ophthalmology, Eye and ENT Hosp of FUDAN Univ, Shanghai, China
  • Jiang Qian
    Ophthalmology, Eye and ENT Hosp of FUDAN Univ, Shanghai, China
  • Mingui Zhang
    Ophthalmology, Eye and ENT Hosp of FUDAN Univ, Shanghai, China
  • Footnotes
    Commercial Relationships Yanqing Zhang, None; Jiang Qian, None; Mingui Zhang, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4614. doi:
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      Yanqing Zhang, Jiang Qian, Mingui Zhang; Improvement of Radiotherapy-induced lacrimal gland injury by IPS cell-derived conditioned medium via inhibition of P38/JNK pathway and cylindromatosis -dependent regulation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4614.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Radiation therapy is one of the most widely used and effective treatment for orbital tumor, but it causes the side effect of dry eye due to lacrimal gland damage. Exploring the mechanisms underlying the secondary injury caused by radiation might be helpful for developing effective radioprotective therapy. The present study investigated the mechanism of the potential radioprotective effect of IPS cell-derived conditioned medium (iPSCM) on gamma-irradiation-induced lacrimal gland failure on experimental mice.

 
Methods
 

Female C57BL/6 mice were irradiated with a total dose of 15 Gy under general anaesthesia. Scintigraphy was performed before irradiation, three days and seven days after irradiation, with a subsequent excision of left side inferior lacrimal gland for histological examination. In the experimental group, conditioned medium from iPSCs (iPSC-CM) were injected through tail vein of the irradiated mice. Primary mouse LGE cell isolation and culture were performed, Gadd45a cDNA was transfected, and cell proliferation was determined. Gadd45a (Millipore), Akt, p-Akt, P38, p-P38, JNK, p-JNK, Erk 1/2 and p-Erk 1/2 were tested by western blot assay.

 
Results
 

iPSCM markedly decrease radiotherapy induced inflammatory processes predominantly through suppressing P38/JNK signaling. Further signalling pathway analyses indicated that iPSC-CM can suppress Akt (Protein Kinase B, PKB) phosphorylation.

 
Conclusions
 

Our study indicates that inhibiting P38/JNK pathway or increasing CYLD might be a therapeutic target in radiation-induced lacrimal gland injury.

 
 
Fig1 iPSCs or iPSC-CM ameliorated Radiotherapy-induced lacrimal injury
 
Fig1 iPSCs or iPSC-CM ameliorated Radiotherapy-induced lacrimal injury
 
 
Fig 2. iPSCs or iPSC-CM abrogated JNK phosphorylation and decreased CYLD and P38 mRNA expression.
 
Fig 2. iPSCs or iPSC-CM abrogated JNK phosphorylation and decreased CYLD and P38 mRNA expression.
 
Keywords: 576 lacrimal gland • 671 radiation therapy • 721 stem cells  
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