# Reversing the ocular impact of NM and SM through novel therapies

> **NIH NIH U54** · NORTHWESTERN UNIVERSITY · 2024 · $493,294

## Abstract

PROJECT SUMMARY/ABSTRACT
The ocular anterior surface in conjunction with the tear film provide the first line of defense against penetration
of noxious agents, which can adversely affect vision. Once this two-component system is breached, the
anterior surface is capable of mounting a vigorous response, which involves a relatively rapid re-
epithelialization along with a brisk inflammatory episode. A variant on the response of the anterior segment to
perturbation occurs to patients following exposure to the chemical warfare agent, sulfur mustard (SM). The
acute symptoms usually resolve completely without further inflammation after 2-6 weeks. However, in a subset
of patients, corneal epithelial erosions, limbal ischemia, and, occasionally, peripheral corneal thinning and
neovascularization may slowly progress. With respect to treatment modalities, either steroidal or non-steroidal
anti-inflammatory drugs are the accepted treatment for the acute and prolonged phases. However, long-term
use of topical steroids in SM ocular injuries is not ideal. Thus, additional therapies to prevent the ocular
deterioration of SM victims is a major unmet need. We have recently demonstrated that topical application
of synthetic, functional high-density lipoprotein nanoparticles (HDL NPs) inherently enhance re-epithelialization
following corneal wounding and can act as anti-inflammatory agents following a chemical burn to the cornea.
Furthermore, HDL NPs are effective vehicles for the delivery of miRNAs to the cornea. Therefore, HDL NPs
will be complexed with miR-184, a highly angiostatic miRNA in the cornea, to treat the delayed phase of NM-
induced corneal injury. We also have evidence that Vitamin D3 (Vit D3) and poly(lactic-co-glycolicacid) immune
modifying nanoparticles (PLGA-IMPs) systemically or HDL NPs topically, administered to mice that were
exposed to topical nitrogen mustard (NM), an analogue of SM, significantly reduce pro-inflammatory and
angiogenic signaling. Collectively, these observations on HDLs, Vit D3, miR-184 and PLGA-IMPs have vast
translational potential as novel treatment modalities for SM-induced injury to the eye. To test this idea, we will
develop and assess these topical ocular therapeutics for the acute and delayed phases of NM injury to mice.
We will evaluate the efficacy and mechanisms underlying these treatments with a combination of clinical,
morphological, cell biological and immunological approaches. Additionally, we will evaluate a new class of HDL
NPs that replace the inorganic Au core with an organic, transparent lipid-conjugated core scaffold, which will
not inhibit the passage of light. We will also appraise the utility of systemic administration of Vit D3 or PLGA-
IMPs to treat the delayed phase of NM-induced ocular injury. These results will establish the most effective
topical and systemic regimens to treat the acute and delayed phases of NM injury. Finally, we will apply this
knowledge to evaluate the efficacy of our chosen ...

## Key facts

- **NIH application ID:** 10907615
- **Project number:** 5U54AR079795-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ROBERT M LAVKER
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $493,294
- **Award type:** 5
- **Project period:** 2021-09-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907615

## Citation

> US National Institutes of Health, RePORTER application 10907615, Reversing the ocular impact of NM and SM through novel therapies (5U54AR079795-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10907615. Licensed CC0.

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