June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
PLGA nanoparticles: a novel class of therapeutics for corneal mustard keratopathy
Author Affiliations & Notes
  • Robert M Lavker
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Fei Yue
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Dan Xu
    microbioilogy/immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Huimin Jiang
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Min Liu
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Nihal Kaplan
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wending Yang
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Venus Onay
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Tobias Neef
    microbioilogy/immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kurt Lu
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Stephen D Miller
    microbioilogy/immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Han Peng
    Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Robert Lavker None; Fei Yue None; Dan Xu None; Huimin Jiang None; Min Liu None; Nihal Kaplan None; Wending Yang None; Venus Onay None; Tobias Neef None; Kurt Lu None; Stephen Miller None; Han Peng None
  • Footnotes
    Support  .EY028560, EY019463, EY032922, AR079795
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3806. doi:
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    • Get Citation

      Robert M Lavker, Fei Yue, Dan Xu, Huimin Jiang, Min Liu, Nihal Kaplan, Wending Yang, Venus Onay, Tobias Neef, Kurt Lu, Stephen D Miller, Han Peng; PLGA nanoparticles: a novel class of therapeutics for corneal mustard keratopathy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3806.

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

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Abstract

Purpose : Sulfur mustard (SM), a chemical warfare agent, can cause severe corneal inflammation and permanent damage to vision in exposed individuals. PLGA nanoparticles (NP) are comprised of poly(lactic-co-glycolic acid) that target circulating inflammatory monocytes and neutrophils in the vasculature, which inhibits them from migrating into inflamed tissues. PLGA NP therapy is effective in a wide range of inflammatory diseases, including the treatment of murine herpes corneal stromal keratitis. Thus, we hypothesized that PLGA NPs would be an innovative means of curtailing the inflammation associated with SM injury.

Methods : Mouse corneas were exposed (1 min) to 0.5% nitrogen mustard (NM), an analog of SM that can mimic perturbations caused by SM. Mice were administrated PLGA NPs i.v., 2hr post wounding, and then daily for 7 days. To assess corneal clarity, corneas were scored for haze. To determine epithelial integrity, corneas were stained with fluorescein and imaged. RT-qPCR was performed to examine expression of pro-inflammatory genes. Whole mount staining with CD31 was conducted to visualize vessel egress into the cornea. Flow cytometry was conducted to characterize the immune cell infiltrate.

Results : NM exposure caused perturbations in the anterior segment including corneal haze, epithelial cell death, extensive corneal neovascularization, and conjunctivalization (e.g., goblet cells in cornea) of the central cornea. A severe inflammation was evidenced by: (i) increased expression of Il1b, Ccl2, Inos, (ii) reduced regulatory T cells, (iii) increased non-inflammatory monocytes, plasmacytoid DC (pDC), and macrophages, and (iv) reduced M2 (iNOS-CD206+) myeloid cells. This suggests that NM compromised the limbal epithelial stem cell niche and caused a significant inflammation due to dysregulation of Treg and myeloid cells. Intravenous injection of PLGA NPs resulted in a decreased orneal haze score (30% reduction) as well as a 50% decrease in expression of cytokines and chemokines (including Il1b, Il6, Inos, Mmp12), indicating a dampening of the corneal inflammation when compared with the vehicle treatment.

Conclusions : We have established a mouse model mimicking SM injured cornea. Our findings strongly suggest that i.v. injection of PLGA NPs have significant potential for treatment of corneal mustard keratopathy as well as other inflammatory conditions.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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