# Myeloid glycolysis in pathological ocular angiogenesis

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2022 · $355,411

## Abstract

PROJECT SUMMARY
Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRDs) are the most common forms of
dementia. Due to the lack of effective approaches for prevention and treatment of these disorders, the toll on
individuals, caregivers and society is currently enormous. Vascular contribution to cognitive impairment and
dementia (VCID) is characterized by the aging neurovascular unit being confronted with, and failing to cope with,
biological insults, resulting in cognitive decline. VCID, defined as an ADRD, is the second most common cause
of dementia after AD and is also a frequent comorbidity with AD. Thus, an in-depth study on VCID will offer a
better understanding of its pathology and consequently will result in novel approaches that improve the
prevention and management of AD/ADRD. Microglia and resident macrophages, important members of the
neurovascular unit, are involved in the early steps of AD/ADRD development and can be identified as potential
therapeutic targets. Recently, metabolic reprogramming including glycolytic switching has been emphasized in
activation of myeloid cells. However, the role of glycolytic reprogramming in microglia/macrophage activation in
VCID has not been explored. Our current NEI-funded Parent project on “Targeting myeloid glycolysis in
pathological ocular angiogenesis” (R01 EY030500-01) aims to uncover the role of Pfkfb3-mediated glycolysis in
macrophages/microglia in pathological retinal angiogenesis. The Parent project focuses on the role of myeloid
glycolysis in retinal dysfunction, especially in pathological vascular growth. Studies in the Parent project have
shown that macrophages/microglia in the retinas of the mouse model of oxygen-induced retinopathy are hyper-
glycolytic, as evidenced by high levels of glycolytic molecules and regulators/activators of glycolysis, including
Pfkfb3. Pfkfb3-mediated glycolysis in macrophages/microglia activates pathways of hypoxic induced factors
(HIFs) and histone acetylation, leading to increased production of pro-inflammatory and pro-angiogenic factors
and subsequent development of dysfunctional vasculature. These results imply a possible role of
microglia/macrophage Pfkfb3-mediated glycolysis in regulating neuroinflammation and cognitive destruction.
Thus, this Supplement application will take advantage of the myeloid Pfkfb3-deficient mouse model generated
from the Parent R01 to uncover the effect of microglia/macrophage glycolysis on neuroinflammation, cerebral
vascular function and cognitive function. Importantly, we will use unbiased system biology approaches such as
light sheet microscopy and single cell RNA sequencing to determine the effect of Pfkfb3-mediated glycolysis on
activation of microglia/macrophage themselves and on other neurovascular unit cells such as endothelial cells,
pericytes, astrocytes and neurons in a well-accepted mouse VCID model. This study will uncover how glycolytic
reprogramming in microglia/macrophage causes dysfunction...

## Key facts

- **NIH application ID:** 10499488
- **Project number:** 3R01EY030500-03S1
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Ruth B Caldwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $355,411
- **Award type:** 3
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499488

## Citation

> US National Institutes of Health, RePORTER application 10499488, Myeloid glycolysis in pathological ocular angiogenesis (3R01EY030500-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10499488. Licensed CC0.

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