June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
The Anti-inflammatory Role of Corneal Epithelium-derived PEDF Via Inhibition of p38 Activation in Dry Eye Disease: In Vivo and In Vitro Study
Author Affiliations & Notes
  • Baikai Ma
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Rongjun Liu
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Chenxi Hu
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Yufei Gao
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Tingting Yang
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Qianqian Lan
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Yiyun Liu
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Tong Sun
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Hong Qi
    Ophthalmology department, Peking University Third Hospital, Beijing, China
    Beijing key laboratory of restoration of damaged ocular nerve, Peking University Third hospital, Beijing, China
  • Footnotes
    Commercial Relationships   Baikai Ma, None; Rongjun Liu, None; Chenxi Hu, None; Yufei Gao, None; Tingting Yang, None; Qianqian Lan, None; Yiyun Liu, None; Tong Sun, None; Hong Qi, None
  • Footnotes
    Support   National Natural Science Foundation of China 81570813
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 159. doi:
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      Baikai Ma, Rongjun Liu, Chenxi Hu, Yufei Gao, Tingting Yang, Qianqian Lan, Yiyun Liu, Tong Sun, Hong Qi; The Anti-inflammatory Role of Corneal Epithelium-derived PEDF Via Inhibition of p38 Activation in Dry Eye Disease: In Vivo and In Vitro Study. Invest. Ophthalmol. Vis. Sci. 2020;61(7):159.

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

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Abstract

Purpose : To find out the expression of pigment epithelium-derived factor (PEDF) in ocular surface and its anti-inflammatory role in dry eye disease (DED).

Methods : A cross-sectional study was conducted with IRB approval. 27 patients with DED and 23 age and sex matched control subjects were enrolled. OSDI questionnaire, Schirmer I test, TBUT and CFS were performed in turn. Tear fluid was collected for detection of inflammatory cytokines (IL-17A, IL-1β, IL-6, IL-8 and TNF-α) and PEDF.
Mix dry eye mouse model was induced. mRNA expression of Pedf in corneal epithelial cells and conjunctiva were quantified by Real-time PCR. Recombinant mouse PEDF or vehicle (PBS) was used to treat dry eye (DE) mice, then tear secretion and CFS were evaluated. mRNA expression of inflammatory cytokines in conjunctiva was quantified.
Human corneal epithelial cells (HCE cells) were treated with isosmotic (310 mOsm) or hyperosmotic media (500 mOsm). After treated by recombinant human PEDF or vehicle (Tris-HCl), mRNA and/or protein expression of IL-1β, IL-6, TNF-α and PEDF were examined by Real-time PCR and ELISA. MAPK signaling pathway (p38, ERK and JNK) and NF-κB p65 were investigated.

Results : Clinical Research: IL-17A, IL-1β, IL-6 and TNF-α in tears of dry eye group (DE group) was higher than that of Normal group (Fig. 1A). Protein level of PEDF is higher in DE group (Fig. 1B). And PEDF in tears correlated with OSDI positively and with TBUT negatively (Fig. 1C).
In vivo study: PEDF was high expressed in corneal and conjunctival epithelium (Fig. 1D). mRNA expression of Pedf in corneal epithelial cells (CEC) other than conjunctiva was up-regulated in DE mice (Fig. 1E). After treated by recombinant PEDF, CFS score of DE mice was decreased (Fig. 2A/2B), mRNA expressions of inflammatory cytokines in ocular tissues were decreased (Il-1β in CEC, Tnf-α in CEC, Il-17a in conjunctiva, Fig. 2C).
In vitro study: mRNA expression of PEDF was increased in hyperosmotic HCE cells (Fig. 1F). After treated by recombinant PEDF, mRNA and/or protein expressions of IL-1β, IL-6 and TNF-α were decreased (Fig. 2D/2E). Phosphorylation of MAPK p38 was increased in 500mOsm and was inhibited under PEDF treatment (Fig. 2F/2G).

Conclusions : Our study elucidated that PEDF in corneal epithelium was up-regulated and it plays an anti-inflammatory role via inhibition of MAPK p38 activation in DED.

This is a 2020 ARVO Annual Meeting abstract.

 

 

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