Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells

Trailokyanath Panigrahi, Shivapriya Shivakumar, Rohit Shetty, Sharon D'souza, Everette Jacob Remington Nelson, Swaminathan Sethu, Nallathambi Jeyabalan*, Arkasubhra Ghosh*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Cornea acts as a structural barrier and protects the eye from environmental stresses. Inflammation in ocular surface causes discomfort and visual distortion. Defective autophagy has been associated with inflammation and ocular surface diseases. Therefore, we explored the protective role of trehalose on inflammation and desiccation-triggered stress in human corneal cells in vitro and in dry eye patients.

Method: TNF-alpha and desiccation stress induced human corneal cells (piHCF and HCE-T) with or without trehalose treatment were analyzed for the expression levels of inflammatory and autophagy related markers by qPCR, western blotting, multiplex ELISA and fluorescence imaging. Dry eye patients (N=9) were enrolled and administered with trehalose in one eye and carboxymethylcellulose (CMC) in the contralateral eye (B.I.D, for 30 days). Dry eye signs OSDI, TBUT, Schirmer's Test, and tear cytokines were measured in dry eye patient's pre and post treatment.

Results: Cells treated with trehalose exhibits increased levels of autophagy markers LC3II and LAMP1 compared to untreated cells. Trehalose reduced the mRNA and secreted cytokines levels of IL-6, IL-8 and MCP-1 in corneal cells under TNF-a and desiccation stress mediated inflammation compared to controls. Further, trehalose reduced stress driven p38 phosphorylation in corneal cells. Additionally, topical administration of trehalose alleviated the clinical symptoms and tears cytokine levels in dry eye patients compared to CMC.

Conclusion: Trehalose reduces stress induced inflammation through p38MAPK inhibition and autophagy activation. The anti-inflammatory mechanism of trehalose was independent to NF kappa B pathway. Further, topical administration of trehalose ameliorated dry eye associated symptoms and associated tear cytokines levels.

Original languageEnglish
Pages (from-to)699-713
Number of pages15
JournalOcular Surface
Volume17
Issue number4
DOIs
Publication statusPublished - Oct 2019

Keywords

  • Corneal inflammation
  • Desiccation stress
  • TNF-alpha
  • Dry eye
  • Autophagy
  • Trehalose
  • NECROSIS-FACTOR-ALPHA
  • DRY EYE DISEASE
  • EPITHELIAL-CELLS
  • TNF-ALPHA
  • KERATOCONUS PATIENTS
  • EXPRESSION
  • APOPTOSIS
  • FIBROBLASTS
  • KERATOCYTES
  • INHIBITION

Fingerprint

Dive into the research topics of 'Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells'. Together they form a unique fingerprint.

Cite this