# Neuronal plasticity in glaucoma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $91,863

## Abstract

PROJECT SUMMARY
Precise connections between synaptic partners are shaped during development to ensure proper neural circuit
function, but how these connections are disassembled and rearranged after injury is less well understood.
Glaucoma provides an excellent model to explore circuit plasticity when a postsynaptic neuron is injured.
Furthermore, the ability to diagnose and treat glaucoma at an optimal stage before irreversible retinal ganglion
cell (RGC) loss occurs requires a comprehensive understanding of inner retina circuit disassembly and
plasticity. However, major gaps exist in knowledge about how RGCs are disconnected from and potentially
rewired with their excitatory presynaptic partners, bipolar cells (BCs), how this remodeling affects RGC
function, and the potential mechanistic role of microglia in circuit disassembly. Such knowledge is required to
successfully develop optic nerve regeneration strategies that depend on functional circuit rewiring. The overall
objective of this application is to determine the connectivity, function, and potential mechanisms of circuit
disassembly and remodeling following intraocular pressure (IOP) elevation. The central hypothesis is that
specific microcircuits in the injured adult retina may exhibit plasticity in terms of connectivity and function, with
microglia playing an important role in synapse pruning. The hypothesis will be tested in the following specific
aims: 1) Determine the specificity and timing of anatomic circuit rewiring in diseased adult retina; 2) Determine
if diseased adult retina has the capacity for functional plasticity; 3) Identify the contributions of microglia in the
mechanism of circuit disassembly. The approach includes biolistic transfection of individual RGCs, sub-micron
imaging, electrophysiological measurements, and novel genetic tools to study bipolar-ganglion cell
connectivity, RGC function, and microglia in experimental rodent glaucoma. The proposal is innovative
because it examines the potential for cell-type specific rewiring, circuit-specific synapse pruning, and functional
plasticity, concepts that shift the paradigm in understanding RGC degeneration in glaucoma. The proposed
research is significant, because the resulting identification of both vulnerable and resilient retinal microcircuits
to target will open new research horizons, particularly in novel psychophysics testing paradigms, drug
development, and RGC regeneration or neuroprotection strategies. Finally, these experiments will
fundamentally expand knowledge of how adult neural circuits react and rearrange in the face of injury.

## Key facts

- **NIH application ID:** 10137719
- **Project number:** 3R01EY028148-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Yvonne Ou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $91,863
- **Award type:** 3
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137719

## Citation

> US National Institutes of Health, RePORTER application 10137719, Neuronal plasticity in glaucoma (3R01EY028148-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10137719. Licensed CC0.

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