TY - JOUR
T1 - Trehalose augments autophagy to mitigate stress induced inflammation in human corneal cells
AU - Panigrahi, Trailokyanath
AU - Shivakumar, Shivapriya
AU - Shetty, Rohit
AU - D'souza, Sharon
AU - Nelson, Everette Jacob Remington
AU - Sethu, Swaminathan
AU - Jeyabalan, Nallathambi
AU - Ghosh, Arkasubhra
N1 - Funding Information:
The authors acknowledge Micro labs Pvt Ltd (to AG and RS), Bangalore, India and Narayana Nethralaya Foundation (Intramural Research grant to NJ and AG) (NNF) for funding this study. We acknowledge the patients and volunteers who participated in the study.
Funding Information:
The authors acknowledge Micro labs Pvt Ltd (to AG and RS), Bangalore, India and Narayana Nethralaya Foundation (Intramural Research grant to NJ and AG) (NNF) for funding this study. We acknowledge the patients and volunteers who participated in the study.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
KW - Corneal inflammation
KW - Desiccation stress
KW - TNF-alpha
KW - Dry eye
KW - Autophagy
KW - Trehalose
KW - NECROSIS-FACTOR-ALPHA
KW - DRY EYE DISEASE
KW - EPITHELIAL-CELLS
KW - TNF-ALPHA
KW - KERATOCONUS PATIENTS
KW - EXPRESSION
KW - APOPTOSIS
KW - FIBROBLASTS
KW - KERATOCYTES
KW - INHIBITION
U2 - 10.1016/j.jtos.2019.08.004
DO - 10.1016/j.jtos.2019.08.004
M3 - Article
SN - 1542-0124
VL - 17
SP - 699
EP - 713
JO - Ocular Surface
JF - Ocular Surface
IS - 4
ER -