July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Sub-Anticoagulant Dose Heparin Dismantles Neutrophil Extracellular Traps (NETs): Therapeutic Implementations for Dry Eye Disease (DED)
Author Affiliations & Notes
  • Jieun Kwon
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • SEUNGWON AN
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Illangovan Raju
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Bayasgalan Surenkhuu
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Anubhav Pradeep
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Christine Mun
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Nour Atassi
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Sandeep Jain
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Jieun Kwon, None; SEUNGWON AN, None; Illangovan Raju, None; Bayasgalan Surenkhuu, None; Anubhav Pradeep, None; Christine Mun, None; Nour Atassi, None; Sandeep Jain, Advaite (I), Alcon (C), Ocugen (C)
  • Footnotes
    Support  NIH Grant EY024966, research to prevent blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 309. doi:
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      Jieun Kwon, SEUNGWON AN, Illangovan Raju, Bayasgalan Surenkhuu, Anubhav Pradeep, Christine Mun, Nour Atassi, Sandeep Jain; Sub-Anticoagulant Dose Heparin Dismantles Neutrophil Extracellular Traps (NETs): Therapeutic Implementations for Dry Eye Disease (DED). Invest. Ophthalmol. Vis. Sci. 2019;60(9):309.

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

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Abstract

Purpose : We have reported that neutrophil extracellular traps (NETs) can contribute to ocular surface pathology in patients with DED. Since heparin dismantles NETs, its use as eye drops may have therapeutic potential in DED. There are numerous reports regarding use of heparin eye drops to treat ocular surface disease such as Ligneous conjunctivitis, therefore safety of heparin eye drop use is established.

Methods : We performed in vitro experiments using cell lines and in vivo experiments using murine corneal epitheliopathy models, and compared the effects of NETs with heparinized NETs. We also performed a retrospective analysis of patients with DED who received Heparin eye drops (100 IU/ml) twice a day.

Results : Sub-anticoagulant dose of Heparin (100 IU/mL) does not delay epithelial wound closure and caused no cytotoxicity whereas anticoagulant doses of heparin (1,000 IU/mL and 10,000 IU/mL) do so. Dismantling of NETs with sub-anticoagulant dose heparin abrogates NET-induced epithelial, fibroblast and T-cell affects in vitro. Application of NETs to murine corneas causes significantly greater epitheliopathy and significantly reduced healing of epithelial defects, whereas application of heparinized NETs significantly abrogates NET-induced murine corneal effects. Heparin eye drops treatment in Patients with DED due to superior limbic keratoconjunctivitis, discordant DED, ocular GVHD, Sjogren syndrome and ocular cicatricial pemphigoid resulted in clinically meaningful reduction of symptoms (OSDI, symptom intensity or SGA) and signs of DED (ocular redness, corneal/conjunctival staining).

Conclusions : Sub-anticoagulant dose heparin (100 IU/mL) eye drop treatment has therapeutic potential in Dry Eye and oGVHD. Our data makes a case for controlled clinical trials to investigate the efficacy of heparin eye drops to treat DED.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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