# Bioluminescent optogenetics to promote axon regeneration

> **NIH NIH R21** · EMORY UNIVERSITY · 2020 · $429,000

## Abstract

The poor recovery from peripheral nerve injuries (PNIs), found in a large number of Americans,
is a significant public health issue. Moderate exercise and brief electrical stimulation have
emerged as the most effective experimental treatments for PNI, but adapting them to patient
use has proven difficult. Bioluminescent optogenetics (BL-OG) uses excitatory luminopsins,
light-sensing ion channels fused with a light-emitting luciferase. When exposed to a cognate
substrate (coelenterazine, CTZ), bioluminescence is generated by the luciferase moiety and the
attached opsin is activated. If injured neurons are induced to express an excitatory luminopsin,
they would be activated by this bioluminescence, stimulating the regeneration of their axons. In
this project we will use BL-OG to treat nerve injuries in a manner that might be used in human
patients. Two critical aspects of that strategy will be addressed now: Investigating the
effectiveness of CTZ administration to excite neurons induced to express an excitatory
luminopsin, using gene therapy after nerve injury, without exacerbating the pain that often
accompanies PNI; and whether this excitation of injured neurons using BL-OG will enhance
axon regeneration when nerve repair is delayed to allow for effective gene therapy. The
bioluminescence produced during BL-OG will be exploited to evaluate the pharmacodynamics
of CTZ in a clinically relevant mouse model of peripheral nerve injury. The effectiveness of
treatment with CTZ on axon regeneration will be studied using electrophysiological and neuro-anatomical outcome measures in a well-established mouse model of peripheral nerve injury. We
anticipate that the results of this exploratory/developmental research will provide a clear
resolution to the fundamental obstacle to advancement of the use of an exciting new
technology.

## Key facts

- **NIH application ID:** 9979122
- **Project number:** 1R21NS113019-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Arthur W. English
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979122

## Citation

> US National Institutes of Health, RePORTER application 9979122, Bioluminescent optogenetics to promote axon regeneration (1R21NS113019-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9979122. Licensed CC0.

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