# Neural Retina-Specific Bim Expression and Hyperoxia Sensitivity of the Developing Retinal Vasculature

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $425,988

## Abstract

Summary
Angiogenesis is required for proper development of the embryonic circulatory system and is an important step
in the progression of many eye diseases, including retinopathy of prematurity (ROP). Therefore, understanding
how the normal regulatory mechanisms in the retina keep angiogenesis in check has great clinical implications.
We recently showed global deletion of Bim, a proapoptotic member of Bcl-2 family of proteins, protects the
developing retinal vasculature from hyperoxia–mediated vessel obliteration and ischemia-mediated
neovascularization in the preclinical mouse model of ROP, the oxygen-induced ischemia retinopathy (OIR)
model. In addition, we showed that targeted deletion of Bim in retinal endothelial cells, pericytes or astrocytes
does not protect the developing retinal vasculature from exposure to hyperoxia–mediated vessel obliteration or
from ischemia-mediated neovascularization. These results strongly support an important role for Bim expression
in retinal inner neurons in proper regulation of developing retinal vasculature. Our hypothesis is that Bim
expression in retinal neurons plays a central role in deriving the sensitivity of developing retinal vasculature to
hyperoxia–mediated vessel obliteration and ischemia–mediated retinal neovascularization during ROP. In Aim
1, we will determine the contribution of Bim expression in the inner retinal neurons to hyperoxia-induced vascular
damage. In Aim 2, we will determine the contribution of VEGF expression in the inner retinal neurons to
hyperoxia-induced vascular damage. Understanding how Bim expression in retinal neurons regulates retinal
vascular development and enhanced sensitivity to hyperoxia will provide insight into Bim mechanisms of action
and aid in the development of alternative ways to modulate retinal angiogenesis.

## Key facts

- **NIH application ID:** 10906285
- **Project number:** 5R01EY032543-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Ismail S Zaitoun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $425,988
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906285

## Citation

> US National Institutes of Health, RePORTER application 10906285, Neural Retina-Specific Bim Expression and Hyperoxia Sensitivity of the Developing Retinal Vasculature (5R01EY032543-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906285. Licensed CC0.

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