# NOT-NS-20-030: Use of anchored biologics to treat vesicant induced neovascularization

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $115,358

## Abstract

We have a long-standing interest in host-pathogen interactions in ocular microbial keratitis with
the ultimate goal of developing better treatment strategies. Severe keratitis is a very damaging
sequela of chemical injuries and causes vision impairment or loss after exposure to sulfur
mustard, which has been used in warfare and by terrorist organizations such as ISIS. This
application is in response to the NOT-NS-20-030 FOA, which is directed to supplement existing
awards to expand research into developing countermeasures to chemical threats including
sulfur mustard exposure, and is in accord with our desire to expand our work to chemically-
induced keratitis.
Corneal vascularization reduces transparency and furthermore drives inflammation by
facilitating entry of various immune cells. Vascularization is therefore an appealing therapeutic
target for treating keratitis. Anti-VEGF biologics have in recent years been remarkably
successful in treating wet age-related macular degeneration and diabetic retinopathy, which
naturally has led to interest in using these reagents to manage corneal neovascularization. The
difficulty is that these biologics, which are soluble macromolecules, are washed out within
minutes when applied topically to the eye and therefore have little or no efficacy. Our solution is
to attach an “anchor” to the biologic i.e. a domain that binds to the cornea and therefore
prevents wash-out. Currently we are using wheat germ agglutinin an anchor, which binds to
GlcNAc and sialic acid that are very abundant on cell surfaces and extracellular matrix. This
prolongs the residency time from a few minutes to at least 24 hours, and we have previously
shown efficacy in a dry eye model by applying an anchored biologic just once daily.
The hypothesis of this study is that targeted inactivation of VEGF using anchored biologics can
prevent neovascularization in chemically challenged mouse corneas. The research plan is to 1)
produce and validate biochemically a wheat germ agglutinin-conjugated antibody to mouse
VEGF, 2) measure effects of application of the anchored antibody on vascularization in vivo in
an established model of neovascularization, and 3) use the procedure to determine the extent
that anchored anti-VEGF antibodies reduces neovascularization in response to nitrogen
mustard. The long-term goal of this supplement is to generate preliminary data to guide further
work and to obtain grant support under the CounterACT program to develop a biologic to block
VEGF for use in humans.

## Key facts

- **NIH application ID:** 10228255
- **Project number:** 3R01EY027331-04S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** ROBERT M SHANKS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $115,358
- **Award type:** 3
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228255

## Citation

> US National Institutes of Health, RePORTER application 10228255, NOT-NS-20-030: Use of anchored biologics to treat vesicant induced neovascularization (3R01EY027331-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10228255. Licensed CC0.

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