# Optogenetic and chemogenetic regulation of uterine vascular function

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2023 · $429,000

## Abstract

PROJECT SUMMARY
Fetal growth restriction (FGR) increases the risk of stillbirth and neonatal death. The adverse effects of being
born FGR extend well beyond the perinatal period, increasing the risk of cardiovascular disease, among others,
in later life. Impaired vascular adaptation to pregnancy is a predominant contributor to FGR. Hypoxic conditions
also alter uteroplacental vascular function, reducing fetal growth, similarly to FGR. To understand the
mechanisms by which an increase in uterine artery (UtA) blood flow can prevent hypoxia-dependent impaired
uterine vasculature and reduced fetal growth, we propose using optogenetics and chemogenetics technology for
manipulating uterine blood flow in live animals. Optogenetics is an innovative technique in which genetically
modified cells express light-activated microbial opsins (e.g., halorhodopsin [NpHR]), which can then be
selectively stimulated by light in vivo. Chemogenetics utilizes modified receptors such as the muscarinic M3
receptor (hM3Dq), which can be selectively activated by specific agonists (e.g., deschloroclozapine [DCZ]). Our
goal is to develop novel and reliable murine models to prevent FGR via endothelium or smooth muscle-specific
mechanisms in the UtA. To address this goal, we propose to conduct two scientific aims. In Aim 1, in mice
expressing NpHR in the smooth muscle, we will address the capacity for light stimulation to vasodilate the UtA
in vivo, increasing UtA blood flow and preventing FGR. Aim 2 will determine the effect of endothelium-dependent
UtA vasodilation via expression of hM3Dq and its selective activation by DCZ locally applied through a
microfluidic channel. Current murine models for increasing UtA blood flow in vivo require pharmacological
activations that are non-tissue specific, and the timing of the activation cannot be controlled. Our optogenetic
and chemogenetic models will provide better control of the degree of blood flow manipulation, enhanced
reproducibility among experiments, improved selectivity of the stimulation, and the opportunity to test the timing
of stimulation. This project will be the first to apply optogenetics and chemogenetics to the vasodilation of UtA in
vivo. Importantly, our proposal can provide the foundation for applying optogenetics and chemogenetics to the
study of other vascular beds in vivo.

## Key facts

- **NIH application ID:** 10785667
- **Project number:** 1R21HD113796-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ramon A Lorca
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2023-09-19 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785667

## Citation

> US National Institutes of Health, RePORTER application 10785667, Optogenetic and chemogenetic regulation of uterine vascular function (1R21HD113796-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10785667. Licensed CC0.

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