Limbal Stem Cell Dysfunction Induced by Severe Dry Eye via Activation of the p38 MAPK Signaling Pathway.

Aug 28, 2023

Experts: Sijie Lin,Minqing Cai,Lingyu Zhang,Yi Mao,Han Wu,Xiaodong Liu,Yixuan Li,Minghui Liang,Xinxuan Cheng,Fei Yu,Hui He,Rongrong Zong,Huping Wu,Zuguo Liu,Shangkun Ou,Wei Li

Severe dry eye (SDE) can cause grievous damage of the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, we established an SDE rat model by removing the extra orbital and infraorbital lacrimal glands and maintained it in a low-humidity environment. One month after the operation, aqueous tear secretion dramatically reduced, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma. The expression of K12 and Pax6 was dramatically down-regulated, while those of K10, Sprr1b, and MUC5AC were up-regulated in the corneal epithelium of the SDE rats. Cell proliferation in the limbal epithelium was up-regulated, while the stem/progenitor marker ABCG2 and the limbal epithelial colony-forming efficiency was decreased under the SDE condition. Furthermore, the p38 MAPK signaling pathway was activated in the limbal corneal epithelium of the SDE rats. The abnormal differentiation and stemness loss in the cornea epithelium could be reversed upon treatment with a p38 inhibitor in SDE in vivo model and in vitro hyperosmolar corneal epithelial culture condition. In conclusion, severe dry eye can lead to limbal stem cell dysfunction, and p38 MAPK signaling pathway activation plays an essential role in this process.
Copyright © 2023. Published by Elsevier Inc.

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ABOUT THE EXPERTS

Sijie Lin,Minqing Cai,Lingyu Zhang,Yi Mao,Han Wu,Xiaodong Liu,Yixuan Li,Minghui Liang,Xinxuan Cheng,Fei Yu,Hui He,Rongrong Zong,Huping Wu,Zuguo Liu,Shangkun Ou,Wei Li

Sijie Lin

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Minqing Cai

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Lingyu Zhang

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Yi Mao

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Han Wu

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Xiaodong Liu

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Yixuan Li

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Minghui Liang

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Xinxuan Cheng

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Fei Yu

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Hui He

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Rongrong Zong

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Huping Wu

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Corneal & Ocular Surface Diseases, Xiamen, Fujian, 361003, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Zuguo Liu

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Corneal & Ocular Surface Diseases, Xiamen, Fujian, 361003, China; Xiang’an Hospital of Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China.

Shangkun Ou

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Corneal & Ocular Surface Diseases, Xiamen, Fujian, 361003, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China. Electronic address: Shangkun_Ou@126.com.

Wei Li

Eye Institute of Xiamen University and affiliated Xiamen Eye Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Corneal & Ocular Surface Diseases, Xiamen, Fujian, 361003, China; Xiang’an Hospital of Xiamen University, Xiamen, Fujian, 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, Fujian, 361102, China. Electronic address: wei1018@xmu.edu.cn.