Pigment epithelium-derived factor (PEDF) plays anti-inflammatory roles in the pathogenesis of dry eye disease.

Abstract

PURPOSE:

To investigate the expression of pigment epithelium-derived factor (PEDF) in ocular surface in dry eye disease (DED) and its anti-inflammatory roles and mechanisms, clinically and by experiments in vivo and in vitro.

METHODS:

A cross-sectional study was conducted to detect the expression of PEDF in tears of dry eye patients by enzyme-linked immunosorbent assay (ELISA). Using dry eye mouse model and human corneal epithelial cells (hCECs) stimulated by hyperosmolarity or inflammatory cytokines, expression of PEDF in corneal epithelial cells, stroma and conjunctiva was quantified by real-time polymerase chain reaction, ELISA and Western blot. Next, either dry eye mice or hyperosmotic hCECs were treated with recombinant PEDF or neutralizing antibodies, and the expressions of inflammatory cytokines and immune cells were detected. Finally, Western blot was performed on MAPK and NF-κB to investigate the signaling pathways by which PEDF played its roles.

RESULTS:

Concentrations of PEDF were increased in tears of dry eye patients. Increased PEDF was observed in corneal epithelial cells (CECs) rather than corneal stroma or conjunctiva in dry eye mice. Furthermore, hCECs exposed to hyperosmolarity showed upregulation of PEDF. In vivo and in vitro studies showed that PEDF suppressed the expression of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17A, as well as the percentage of Th17 cells in DED. Further investigation showed that PEDF inhibited the phosphorylation of MAPK p38 and JNK in hyperosmotic hCECs.

CONCLUSIONS:

CECs derived PEDF is increased in DED. PEDF plays anti-inflammatory and immunoregulatory roles in the pathogenesis of DED.

• Authors: Baikai Ma, Yifan Zhou, Rongjun Liu, Kai Zhang, Tingting Yang, Chenxi Hu, Yufei Gao, Qianqian Lan, Yiyun Liu, Xiulan Yang, Hong Qi
• Journal: The ocular surface (Ocul Surf) Vol. 20 Pg. 70-85 (04 2021) ISSN: 1937-5913 [Electronic] United States
• PMID: 33412338 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Eye Proteins
• Nerve Growth Factors
• Serpins
• pigment epithelium-derived factor

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cross-Sectional Studies
• Cytokines
• Dry Eye Syndromes (drug therapy)
• Enzyme-Linked Immunosorbent Assay
• Epithelium, Corneal
• Eye Proteins
• Humans
• Mice
• Nerve Growth Factors
• Serpins