# The Mechanism of Immune-Vascular Crosstalk in Retinopathy

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2022 · $388,045

## Abstract

PROJECT SUMMARY/ABSTRACT
Retinopathy of prematurity (ROP) is a major cause of blindness and disability in children. With advances in
neonatal care, smaller and more premature infants are saved who are at high risk for ROP. Therefore, the
incidence of ROP continues to increase. Ablation surgery destroys retina and anti-Vascular endothelial growth
factor (VEGF) treatment may cause systemic suppression of vessel growth in fragile neonates. The long-term
goal is to understand the molecular mechanisms of ROP development to devise earlier preventative therapies.
Inflammation and changes in immune function are clearly involved in ROP, but standard anti-inflammatory drugs
such as steroids or NSAIDS are not effective in ROP and the way to control inflammation is not clear. However,
immune cells are a source of cytokines and growth factors that may interact with the endothelial cells and contribute
to the development of structural and functional abnormalities of the vessel wall. There is increasing evidence for the
critical role of myeloid cells in retinal vascular development, remodeling, repair, and anastomosis. Myeloid cells such
as microglia, are rapidly activated after an inflammatory insult and modulate angiogenesis. The overall objective in
this application is to identify the mechanism of immune-vascular interaction in retinopathy. Understanding of
pathological immune changes in the retinopathy is currently limited by a relative paucity of information about the
physiology and function of resident immune cells in the healthy eye. Suppressor of cytokine signaling 3 (SOCS3) is
a critical regulator that controls innate and adaptive immunity, tissue inflammation, cytokine production, and
macrophage polarization, we reported that SOCS3 can suppress pathological ocular angiogenesis, therefore,
SOCS3 is an essential immune-regulator that mediates immune-vascular interaction in ocular neovascularization
formation. We found loss of SOCS3 in immune cells of myeloid origin significantly increased pathological retinal
neovascularization in oxygen-induced retinopathy modeling ROP. We hypothesize that myeloid SOCS3 regulates
immune-vascular crosstalk through modulating retinal inflammation, immune cell activation and recruitment to
control retinopathy. The rationale for the proposed research is that understanding the molecular mechanisms of
ROP development has the potential to develop treatment of ROP that now affects ~16,000 US infants per year.
We will test this hypothesis with three Aims. Aim 1: To determine if myeloid SOCS3 controls pathological retinopathy;
Aim 2: To determine if myeloid SOCS3 controls retinopathy through modulating the recruitment and activation of
immune cells into the retina; Aim 3: To determine if myeloid SOCS3 controls immune-vascular crosstalk through
modulation of retinal inflammatory proteins. The proposed research is innovative because it represents a
substantive departure from the status quo by identifying the molecular mechanisms o...

## Key facts

- **NIH application ID:** 10400041
- **Project number:** 5R01EY030140-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** YE SUN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,045
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400041

## Citation

> US National Institutes of Health, RePORTER application 10400041, The Mechanism of Immune-Vascular Crosstalk in Retinopathy (5R01EY030140-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10400041. Licensed CC0.

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