# Mechanism of intravitreal VEGF-A165a and topical calcitriol for the treatment of retinopathy of prematurity

> **NIH NIH K08** · UNIVERSITY OF ROCHESTER · 2022 · $236,144

## Abstract

PROJECT SUMMARY
Dr. Olachi Mezu-Ndubuisi is a neonatologist with a background training as an optometrist, now an Assistant
Professor of Pediatrics with an affiliate appointment in the Department of Ophthalmology at University of
Wisconsin (UW). She combines these experiences in her research studying Retinopathy of Prematurity (ROP).
ROP is a bi-phasic disease of abnormal retinal vascularization in premature infants, characterized by
dysregulation of vascular endothelial growth factor (VEGF). ROP has no cure, and existing therapies have
adverse systemic effects and long-term deficits. Dr. Mezu-Ndubuisi developed a non-invasive method of
visualizing retinal blood vessels in a mouse model of oxygen-induced retinopathy (OIR) using fluorescein
angiography. She correlated in vivo retinal vascular changes (arterial tortuosity, venous dilation, and capillary
vascularity) to structure and function, and performed histological studies to show unique long-term features of
OIR mice, such as prolonged cellular apoptosis, glial activation, and ectopic formation of synapses. Having
defined the in vivo and histologic OIR phenotypes, she seeks to use molecular techniques to enhance
understanding of VEGF regulation in ROP in order to develop safe and effective therapies. In her preliminary
studies, there was a 6-fold increase in total mouse Vegfa164 levels at post-natal day (P) 13, early in Phase 2
ROP, in OIR mice compared to RA mice, and Vegfa164b showed a 1.3-fold higher trend in OIR than RA mice at
P10 (peak of retinal vaso-obliteration during hyperoxia). This suggests that an imbalance of VEGF isoforms
occurs in ROP. She then administered the pro-angiogenic isoform of VEGF-A165, VEGF-A165a, in sustained
release microparticles which resulted in earlier retinal revascularization with improved arterial tortuosity and vein
dilation. She next compared topical calcitriol (active form of vitamin D) eyedrop to intraperitoneal (IP) calcitriol
and both inhibited retinal angiogenesis later in Phase 2 ROP, but topical calcitriol did not cause growth restriction
like IP calcitriol. Dr. Mezu-Ndubuisi hypothesizes that using intravitreal VEGF-A165a early in Phase 2 and topical
calcitriol later in Phase 2, would rescue the abnormal OIR in vivo and histologic phenotypes. In this K08, Dr.
Mezu-Ndubuisi will determine the most effective and least toxic dose of intravitreal VEGF microparticles or free
intravitreal VEGF protein and topical calcitriol in Phase 2 ROP (Aim 1), and then study the molecular mechanisms
by which VEGF-A165a and calcitriol regulate angiogenic signaling in ROP (Aim 2). UW provides an excellent
academic environment, state-of-the-art facilities, and academic resources dedicated to Dr. Mezu-Ndubuisi’s
success. She has strong intra-mural and extra-mural mentoring from well-established NIH investigators and
experts in ROP, molecular genetics, angiogenesis, and Vitamin D. Dr. Mezu-Ndubuisi’s career goals and
objectives include a detailed training plan to increase...

## Key facts

- **NIH application ID:** 10645643
- **Project number:** 7K08EY032203-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Olachi Joy Mezu-Ndubuisi
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $236,144
- **Award type:** 7
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645643

## Citation

> US National Institutes of Health, RePORTER application 10645643, Mechanism of intravitreal VEGF-A165a and topical calcitriol for the treatment of retinopathy of prematurity (7K08EY032203-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10645643. Licensed CC0.

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