June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Vitamin D3 and HDL nanoparticles: novel ocular therapeutics for the acute inflammatory response following mustard exposure
Author Affiliations & Notes
  • Han Peng
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Nihal Kaplan
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Andrea E Calvert
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kaylin M McMahon
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Junyi Wang
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wending Yang
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Venus Onay
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kurt Lu
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Colby Shad Thaxton
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Robert Lavker
    Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Han Peng, None; Nihal Kaplan, None; Andrea Calvert, None; Kaylin McMahon, None; Junyi Wang, None; Wending Yang, None; Venus Onay, None; Kurt Lu, None; Colby Thaxton, None; Robert Lavker, None
  • Footnotes
    Support  NIH Grants EY06769, EY017539, EY019463, AR064144 and AR071168, Dermatology Foundation , Eversight Eye Bank research grants, the Prostate Cancer Foundation, the Center for Regenerative Nanomedicine (CRN), and the Nanyang Technological Institute-Northwestern University (NTU-NU) Institute for Nanomedicine
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1305. doi:
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      Han Peng, Nihal Kaplan, Andrea E Calvert, Kaylin M McMahon, Junyi Wang, Wending Yang, Venus Onay, Kurt Lu, Colby Shad Thaxton, Robert Lavker; Vitamin D3 and HDL nanoparticles: novel ocular therapeutics for the acute inflammatory response following mustard exposure. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1305.

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

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Abstract

Purpose : The eye is the most susceptible part of the body to the effects of chemical warfare agents, nitrogen and sulfur mustard (NM and SM). Steroidal and/or non-steroidal anti-inflammatory drugs are the accepted treatments for the acute and prolonged phases of mustard injury. However, there have been warnings against the use of topical steroids in SM ocular injuries. Thus, additional therapies to prevent the SM-induced ocular deterioration is a major unmet need.

Methods : Mouse corneas were exposed to NM (2%, 5 min) an analogue of SM. After exposure, corneas were topically treated with high-density lipoprotein like nanoparticles (HDL NPs), or Vitamin D3 (Vit D3, 5 ng i.p.) that was systemically injected. Cy3-labeled HDL NPs were used to determine penetration of HDL NPs through corneal epithelium. To evaluate corneal clarity, mouse corneas were imaged for haze scoring. To determine epithelial integrity, corneas were stained with fluorescein and imaged. Immunonstaining and qPCR were performed to examine gene expression.

Results : After NM exposure, Vit D3 treatment significantly (>60%) reduced: (i) the amount of corneal fluorescein staining; (ii) degree of haze; (iii) pro-inflammatory cytokine and chemokine expression; and (iv) angiogenic signaling. This indicates that Vit D3 treatment results in marked alleviation of NM-induced corneal damage. Furthermore, we have demonstrated that following topical treatment, HDL NPs can penetrate into corneal epithelial cells. After NM injury, topical treatment of HDL NPs (1μM) significantly attenuated the expression of several inflammatory factors including Il6, Il1b, Cox2, and Ccl2. Additionally, factors that affect the stroma and normal repair process were reduced including Mmp9, Mmp12, Vegfa, Tgfb, and Pdgfb.

Conclusions : Collectively, our findings strongly suggest that systemic delivery of Vit D3 or topical delivery of HDL NPs to the cornea and limbus have vast treatment potential for corneal mustard keratopathy. Furthermore, the beneficial properties of HDL NPs as well as Vit D3 argues for the development of a “super” HDL NP-Vit D3 eye drop in order to reduce inflammation in the anterior segment.

This is a 2021 ARVO Annual Meeting abstract.

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