June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Mechanism associated with acrolein’s toxicity to the cornea in vitro
Author Affiliations & Notes
  • Suneel Gupta
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States
  • Nishant Rajiv Sinha
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States
  • Praveen Balne
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States
  • Ratnakar Tripathi
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States
  • Nathan Hesemann
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    MU Health Care Mason Eye Clinic-University Hospital, Columbia, Missouri, United States
  • Prashant R. Sinha
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States
  • Rajiv R Mohan
    Harry S Truman Memorial Veterans' Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Suneel Gupta, None; Nishant Sinha, None; Praveen Balne, None; Ratnakar Tripathi, None; Nathan Hesemann, None; Prashant Sinha, None; Rajiv Mohan, None
  • Footnotes
    Support  National Eye Institute, NIH, Bethesda, Maryland (5R21EY030233) Grant (R.R.M.); partially by a pilot grant (S.G.) from the Truman VA Medical Research Foundation, Columbia, Missouri; National Eye Institute, NIH, NEI, Bethesda, Maryland (5R21EY030234; 5R01EY017294; and 1R01EY030774) Grants (R.R.M.); the United States Veterans Health Affairs, Washington, DC, (1I01BX000357) Merit grant; and RCS award (R.R.M.).
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 942. doi:
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      Suneel Gupta, Nishant Rajiv Sinha, Praveen Balne, Ratnakar Tripathi, Nathan Hesemann, Prashant R. Sinha, Rajiv R Mohan; Mechanism associated with acrolein’s toxicity to the cornea in vitro. Invest. Ophthalmol. Vis. Sci. 2021;62(8):942.

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

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Abstract

Purpose : Acrolein, a volatile organic compound, was used as a warfare agent in World War I and has the potential viable public threat worldwide. Recently, we studied the impact of acrolein exposure to the cornea and other ocular surface tissues in vivo using a rabbit model. The study sought to uncover the mechanisms of acrolein’s toxicity to the cornea using an in vitro model.
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Methods : Primary human corneal stromal fibroblasts cultures (h-CSFs) from donor human corneas were used. Presto blue and MTT assays were used to determine the dose of acrolein, N-acetyl cysteine (NAC), and Buthionine sulphoximine (BSO) for h-CSFs. Different biochemical assays using standard commercial kits and qRT-PCR analysis were performed to understand the mode of acrolein toxicity.

Results : The MTT and PrestoBlue assays defined that 100 µM dose of acrolein represents IC50, for h-CSFs an acute level at 4h (p<0.001). The biochemical assays revealed that acrolein exposure to h-CSFs led to oxidative stress and a compromised level of glutathione. These biochemical variations led to mitochondrial dysfunction via changes in the mitochondrial membrane potential (ΔΨm). The mRNA data, TUNEL, and caspase-3/7 assays showed that acrolein induces apoptosis in h-CSFs. Treatment with NAC; a precursor of glutathione, in h-CSFs decreased the oxidative stress, elevated the GSH level, regulated the mitochondrial membrane potential (ΔΨm), and rescued h-CSFs from apoptosis under acrolein-exposed conditions.
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Conclusions : Acrolein’s exposure to human corneal fibroblasts induced alterations in phenotype, and cell death through oxidative damage at least in part of toxicity, in vitro.

This is a 2021 ARVO Annual Meeting abstract.

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