July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Acrolein exposure to eye causes corneal inflammation, fibrosis, and angiogenesis
Author Affiliations & Notes
  • Suneel Gupta
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Opthalmology, College of Veterinary Medicine,, Univeristy of Missouri, Columbia, Missouri, United States
  • Michael K Fink
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Opthalmology, College of Veterinary Medicine,, Univeristy of Missouri, Columbia, Missouri, United States
  • Ratnakar Tripathi
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Opthalmology, College of Veterinary Medicine,, Univeristy of Missouri, Columbia, Missouri, United States
  • Prashant R Sinha
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Opthalmology, College of Veterinary Medicine,, Univeristy of Missouri, Columbia, Missouri, United States
  • Shyam S Chaurasia
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Opthalmology, College of Veterinary Medicine,, Univeristy of Missouri, Columbia, Missouri, United States
  • Elizabeth A Giuliano
    Opthalmology, College of Veterinary Medicine,, Univeristy of Missouri, Columbia, Missouri, United States
  • Nathan Hesemann
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institutue, University of Missouri, Columbia, Missouri, United States
  • Lindsey McDaniel
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institutue, University of Missouri, Columbia, Missouri, United States
  • Emilee M Dailey
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institutue, University of Missouri, Columbia, Missouri, United States
  • Rajiv R Mohan
    Harry S Truman Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institutue, University of Missouri, Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Suneel Gupta, None; Michael Fink, None; Ratnakar Tripathi, None; Prashant Sinha, None; Shyam Chaurasia, None; Elizabeth Giuliano, None; Nathan Hesemann, None; Lindsey McDaniel, None; Emilee Dailey, None; Rajiv Mohan, None
  • Footnotes
    Support  RO1EY17294
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 151. doi:
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    • Get Citation

      Suneel Gupta, Michael K Fink, Ratnakar Tripathi, Prashant R Sinha, Shyam S Chaurasia, Elizabeth A Giuliano, Nathan Hesemann, Lindsey McDaniel, Emilee M Dailey, Rajiv R Mohan; Acrolein exposure to eye causes corneal inflammation, fibrosis, and angiogenesis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):151.

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

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Abstract

Purpose : Acrolein exposure to eye causes severe corneal damage and vision loss due to its strong irritant and vesicant properties. Acrolein is a key chemical used for producing many commercial products. In addition, it is present in wildfire smoke and was used as a chemical weapon in World War I, and recently in Syria. This study aimed to identify factors mediating acrolein’s toxicity to the cornea and potential targets for mitigating its effects in vitro and in vivo rabbit models.

Methods : New Zealand White rabbits, human corneal fibroblasts (HSF), epithelial cells (HCE), and donor human corneas were used. Rabbit eyes were exposed to acrolein vapor using customized delivery method. Serial slit-lamp biomicroscopy and clinical eye exams were performed to analyze ocular inflammation, toxicity, and corneal pathology in live animals. Protein lysates and mRNA isolated from cell lysates and ocular tissues were used for biochemical, molecular, and gene expression studies. Frozen corneal tissue sections were used for H&E and immunofluorescence to analyze infiltrating immune cells and acrolein’s toxicity to the cornea.

Results : Acrolein-vapor showed dose- and time-dependent damage to cornea, eyelids, and sclera. The clinical slitlamp exams in live rabbits showed severe inflammation, redness, swelling and ocular fluid discharge in early time points. High doses or extended exposure of acrolein caused severe morbidity to ocular tissues characterized by corneal fibrosis and neovascularization and dramatically increased expression of profibrotic, proangiogenic and inflammatory factors such as TGFβ, VEGF, and IL6 respectively (up to 7 fold; p <0.05). Further, acrolein-treated eyes showed significantly increased levels of reactive oxygen species (ROS) (7.1 fold; p<0.01), compromised glutathione (GSH) (2.4 fold; p<0.01) and enhanced TUNEL+ apoptotic cells (6.8 fold; p<0.01) compared to vehicle-treated control eyes. Acrolein treatment to HSF and HCE showed time- and dose-dependent toxicity. A single 100µM dose produced high toxicity at 2h and 10µM dose caused delayed toxicity (24h) characterized by morphological changes, elevated ROS levels (8.7-fold; p<0.01), and reduced GSH levels (4.8 fold; p<0.01). Similar trends were observed in human cornea ex-vivo model.

Conclusions :
Acrolein-induced corneal blindness in vitro and in vivo is mediated by inflammatory, profibrotic, and proangiogenic cytokines.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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