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

Panigrahi, Trailokyanath; Shivakumar, Shivapriya; Shetty, Rohit; D’Souza, Sharon; Nelson, Everette Jacob Remington; Sethu, Swaminathan; Jeyabalan, Nallathambi; Ghosh, Arkasubhra

doi:10.1016/j.jtos.2019.08.004

Cited by 49 publications

(42 citation statements)

References 40 publications

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“…Our findings are consistent with previous studies using primary HCECs but contrast somewhat with results by Panigrahi and colleagues, 56 who reported autophagy induction by trehalose via increased phosphorylation of Akt with higher protein levels of P62 in corneal epithelial cells exposed to desiccation stress. This discrepancy regarding the mechanism of trehalose may be due to the utilization of different cell types and different stress models.…”

Section: Discussionsupporting

confidence: 90%

“…52,55 This study confirms previous findings and further reveals that the addition of trehalose was found to reduce secreted cytokine levels in primary HCECs exposed to hyperosmotic stress, suggesting that trehalose may be acting on the intracellular signaling pathways, thereby reducing the levels of inflammatory markers. 34,56 However, higher concentrations (2.0%-5.0 %) of trehalose appeared to lose the protective effects in a concentration-dependent manner, and 5.0% trehalose may stimulate higher expression of these inflammatory markers, as the accumulation of trehalose increased osmolarity in deionized water, SHEM, and the hyperosmolar medium. The optimum concentration, then, was 1.0% trehalose.…”

Section: Discussionmentioning

confidence: 99%

“…This discrepancy regarding the mechanism of trehalose may be due to the utilization of different cell types and different stress models. Panigrahi et al 56 used a SV40 large T antigen immortalized HCE cell line (HCE-T), which may respond to trehalose differently than our primary HCECs. Their desiccation stress model was created by air-drying HCE-T cultures for 10 minutes at room temperature with 40% humidity after the medium completely aspirated, which is a seriously dry condition that could cause cell damage or even death.…”

Section: Discussionmentioning

confidence: 99%

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Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress

Liu

Chen

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress

Liu

Chen

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…12 Similarly, defective autophagy has been associated with inflammation in ocular surface diseases. [13][14][15] Defective autophagy associated with lacritin monomer deficiency in dry eye may cause a loss of ocular surface homeostasis, and this was reversed by topical lacritin in a dry eye mouse model. 14 Autophagy increases cellular stress tolerance thereby increasing the threshold for cellular apoptosis using several mechanisms, including the selective removal of damaged, apoptosis-inducing mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Commercially Available Eye Drops Containing Trehalose Protect Against Dry Conditions via Autophagy Induction

Hernández

Taisne

Lussignol

et al. 2021

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Evaluation of marketed eye drops with or without trehalose, a nonreducing natural osmoprotector disaccharide, in autophagy modulation and its role in cell survival during desiccation. Materials and Methods: Eye drops containing either sodium hyaluronate (SH) (Hyabak Ò , Thea, France) or a combination of SH with trehalose (Thealose Duo Ò , Thea, France) were compared with control conditions to evaluate the ability to modulate autophagy in human epithelial cells in vitro. Autophagy was monitored using LC3, a marker of the autophagic machinery, by fluorescence microscopy and immunoblot analysis. Control and autophagy-deficient cells treated with eye drops were exposed to desiccation to mimic dry eyes and cell survival was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Trehalose, a known autophagy inducer was used as a positive control. Results: Artificial tears containing SH with and without trehalose induce a complete autophagic flux, as indicated by an increase in the number of autophagosomes and autolysosomes, and the accumulation of the lipidated form of LC3 associated with complete autophagy. In addition, there was a synergistic effect of SH for autophagy induction when combined with trehalose, compared with each of the components alone. Survival of cells treated with both eye drops and exposed to desiccation was decreased in autophagy-deficient cells, demonstrating the essential role of autophagy on eye drop protection. Conclusions: Autophagic flux is induced by SH-containing eye drops, and this phenomenon is enhanced in combination with trehalose. We also demonstrated that autophagy induction is involved in the osmoprotective effects of both trehalose and SH-containing eye drops, to maintain epithelial cell homeostasis in dry conditions.

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“…[ 14 ] Desiccation stress also increases the inflammatory factors' level in human ocular surface epithelial cells. [ 15 16 ] These factors can serve as an itch stimulus further perpetuating eye rubbing and amplify the inflammatory response to result in a clinical presentation of ocular surface inflammation with noninfectious or unknown etiology. Besides reducing the proliferative capacity and inducing apoptosis,[ 10 ] alcohol can reduce the mucosal immune response on the ocular surface due to its immune-suppressive properties.…”

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confidence: 99%

Sanitizer aerosol-driven ocular surface disease (SADOSD)—A COVID-19 repercussion?

Shetty

Jayadev

Chabra

et al. 2020

Indian J Ophthalmol

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Since the onset of the COVID-19 pandemic, there has been an advisory for regular and thorough cleaning of hands besides other measures such as social distancing and self-isolation. The rationale for the same is to prevent the transfer of the virus from hands that have come in contact with fomites. While both alcohol-based hand rubs (ABHR) or washing with soap and water are claimed to have been effective, hand sanitizers have gained more popularity due to the ease of use. The increased frequency of ABHR use and the aerosols generated pose a potential threat to the skin and exposed mucosal surfaces, especially that of the eye due to the proximity of use. The adverse effects of alcohol in these sanitizers can be manifold. An allergic or inflammatory response can occur depending on the predisposing or preexisting conditions. This article describes the risks, underlying mechanisms, and preventive measures for sanitizer aerosol-driven ocular surface disease.

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

Cited by 49 publications

References 40 publications

Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress

Trehalose Induces Autophagy Against Inflammation by Activating TFEB Signaling Pathway in Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress

Commercially Available Eye Drops Containing Trehalose Protect Against Dry Conditions via Autophagy Induction

Sanitizer aerosol-driven ocular surface disease (SADOSD)—A COVID-19 repercussion?

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