# Antigen-independent suppression of ocular angiogenesis via the Fc receptor

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $403,750

## Abstract

Abstract
Aberrant angiogenesis, a process of new blood vessel formation, is implicated in a variety of
diseases that affect nearly 10% of the world’s population. In new and exciting work, we made the
surprising observation that human IgG1, as a class, suppresses multiple models of ocular and
non-ocular angiogenesis in mice and cells independent of their actual target. This target-
independent angiostatic effect is mediated through FcγRI receptor signaling. Given the
abundance of IgG1 proteins in the blood, as well as their widespread therapeutic use, our findings
assume broad importance in better understanding the full range of the biological effects of
antibodies. The extent and precise mechanisms of IgG/Fc receptor modulation of the vasculature
remain to be deciphered. Therefore, it is critical to define the immunological molecular signaling
pathways responsible for mediating the angioinhibitory effects of human IgG1/FcγRI ligation. It is
also important to delineate the influence of therapeutic FcγRI-binding proteins on the cell types
and molecular pathways involved in aberrant angiogenesis. In addition to advancing the
fundamental biology of IgG/Fc-mediated angiosuppression, our findings may also address a
significant ophthalmic need by improving existing IgG1-containing medicines. To that end, we will
determine whether a rationally guided re-dosing or reformulation of bevacizumab, a full-length
humanized IgG1 antibody, can substantially improve its therapeutic efficacy by exploiting this
newly discovered anti-angiogenic activity, which is separate from VEGFA neutralization. In order
to accomplish these goals, we propose to perform detailed studies in models that better mimic
the human vascular and immune systems. We will utilize mouse (including humanized) models
of corneal and choroidal neovascularization to provide novel functional and molecular insights
into how IgG1/FcγRI signaling contributes to modulation of angiogenesis. Findings from this
project will help illuminate innovative molecular basis of the vasculature that can be targeted in
the multitude of ocular pathologies caused by abnormal vessel growth. As such, this proposal is
aligned with the dual goals of the Retinal Diseases and Immunology Programs of NEI's Vision
Research: Needs, Gaps, and Opportunities Strategic Plan.

## Key facts

- **NIH application ID:** 9968411
- **Project number:** 5R01EY028027-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jayakrishna Ambati
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968411

## Citation

> US National Institutes of Health, RePORTER application 9968411, Antigen-independent suppression of ocular angiogenesis via the Fc receptor (5R01EY028027-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968411. Licensed CC0.

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