# Defining Roles of Perivascular Retinal Neurons by Integrating Visual Stimuli and Vascular Tones

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $116,888

## Abstract

PROJECT SUMMARY/ABSTRACT
 Retinal neurons wire to circuits to transmit processed light stimulations into electrical signals before passing
them onto the brain. Beyond interneurons, retinal ganglion cells (RGCs) also interact with nearby non-neuronal
cells, such as glial cells, vessels, and circulating microglia, forming a microenvironment. Beyond the traditional
view of presynaptic inputs, how the local microenvironment modulates RGC signal processing remains largely
unknown. Given the compact space within the inner retina, my central hypothesis is that specific RGC subsets
may selectively interact with nearby non-neuronal cells, such as vascular endothelial cells, which may modulate
neuronal signal processing. Primarily in the retina, light stimuli are not the only sensory stimuli; other modulations,
such as temperature, ocular or vascular pressures, and neurochemical stimulation, may also have specific
impacts on RGC signal processing. Notably, the RGCs can extract different types of stimuli and optimize
information processing to efficiently send integrated information to the brain. My preliminary data demonstrated
that beyond the traditional inputs from presynaptic interneurons (bipolar cells and amacrine cells), one group of
RGCs is located near the blood vessels with perivascular endfeet. These perivascular RGCs also express Piezo2
- a mechanosensitive channel. Thus, they may be the primary neurons in the retina that not only respond to light
stimuli but also to mechanical stimulations. The innovation of this study is to study how mechanosensitive
channels affect the light response of some perivascular RGCs. Additionally, I propose exploring the role of Piezo2
in modulating perivascular RGCs between normal conditions and optic neuropathy models. This proposal aims
to study the interaction of perivascular RGCs with blood vessels via mechanosensitive channels. I will use
electrophysiology, pharmacology, genetics, viral tools, single-cell sequencing, and in vivo imaging to achieve
these goals. In Aim 1, I will study how Piezo2 channels affect the visual function of the perivascular RGCs. In
Aim 2, I will investigate the neuroprotection role of perivascular RGCs in different retinal diseases mediated by
Piezo2. At my independent laboratory (Aim 3), I will establish an intraocular imaging platform to enhance the
findings using non-invasive, real-time in vivo imaging. The proposed work is significant since results from this
study may uncover novel neurovascular protective mechanisms against degeneration and lead to new strategies
for intervention. My long-term goal is to understand the visual circuit assembly in the retina at single-neuron type
resolution to establish a roadmap to understand how the retina's visual features are detected and interpreted by
the brain. Additional training obtained during this award in visual system development (with Dr. Xin Duan),
mechanosensitive channel (with Dr. Yuh Nung Jan), and retinal disease (with Dr. Yang Hu...

## Key facts

- **NIH application ID:** 10950258
- **Project number:** 1K99EY036489-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Fei Wang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $116,888
- **Award type:** 1
- **Project period:** 2024-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950258

## Citation

> US National Institutes of Health, RePORTER application 10950258, Defining Roles of Perivascular Retinal Neurons by Integrating Visual Stimuli and Vascular Tones (1K99EY036489-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10950258. Licensed CC0.

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