June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Comparison of Cellular Cytotoxicity Induced by Dry Eye Conditions by Formulations of Cyclosporine.
Author Affiliations & Notes
  • Arun Balasubramaniam
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Dhara Shah
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Yongbeom Seo
    Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
  • Kyung-No Son
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Marwan Ali
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Sushma Kalmodia
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Hyunjoon Kong
    Bioengineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States
  • Vinay Kumar Aakalu
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Arun Balasubramaniam, None; Dhara Shah, None; Yongbeom Seo, None; Kyung-No Son, None; Marwan Ali, None; Sushma Kalmodia, None; Hyunjoon Kong, None; Vinay Aakalu, Horizon Pharma (C), University of Illinois at Chicago (P)
  • Footnotes
    Support  VA I01BX004080, DOD W81XWH-17-1-022, NIH/NEI R01EY029409, NIH/NEI K08EY024339
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 147. doi:
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      Arun Balasubramaniam, Dhara Shah, Yongbeom Seo, Kyung-No Son, Marwan Ali, Sushma Kalmodia, Hyunjoon Kong, Vinay Kumar Aakalu; Comparison of Cellular Cytotoxicity Induced by Dry Eye Conditions by Formulations of Cyclosporine.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):147.

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

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Abstract

Purpose : Dry eye disease (DED) is a complex disease characterized by ocular surface inflammation and increases in tear osmolarity. For several years, the Cyclosporine-A (CysA) castor-oil emulsion, Restasis®, has been a frequently used therapy and could be considered one of the gold-standards of therapy. CysA is known to pose challenges for ophthalmic formulation, due to its hydrophobicity and low aqueous solubility, necessitating the use of emulsions or other non-standard formulation methods. In developing new DED therapies, it may be of interest to investigators to benchmark new agents to Restasis®. Although clinical data and some in vivo data are available, limited published work exists on the effects of Restasis® in vitro. In this study we investigated the cytoprotective effects of Restasis®, CysA in DMSO, a novel castor-oil nanoemulsion (with and without CysA), and an castor-oil containing artificial tear (Refresh Optive Advanced® with and without CysA) when immortalized human corneal epithelial cells (HCE) were exposed to hyperosmolar (Hosm) conditions.

Methods : Cell Viability Assays
HCE cells were seeded at 3x104 / well in a 96-well plate. NaCl was added to the media to create a toxic hyperosmolar state. Several therapeutic articles and controls were then tested, in a co-treatment fashion. Cell viability was assessed using tetrazolium salt based assays (WST-1 (Roche) over several time points. The absorbance was measured using a microplate reader (Biotek Synergy H1, Winooski WI) at 450/655 nm and the percent cell viability was calculated. Statistical comparisons between controls and tested articles were then performed.

Results : We found that cellular toxicity induced by Hosm was abrogated by all tested articles, with CysA alone having the least effect. Moreover, castor-oil emulsions alone had the ability to reduce cellular toxicity. Restasis® and emulsions containing CysA also reduced cellular toxicity.

Conclusions : The results of these experiments can be used for future in vitro drug development studies as a benchmark for the efficacy of Restasis®. Moreover, these data support new avenues for the study of the efficacy of alternative castor-oil nanoemulsions in conditions mimicking DED.

This is a 2020 ARVO Annual Meeting abstract.

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