# Optogenetic Vision Restoration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $380,725

## Abstract

Over 100,000 Americans of all ages suffer from inherited retinal diseases (IRD), which cause a progressive loss of vision. In most IRDs, disease begins in the rods, causing vision loss from the periphery to the center, leaving patients unable to navigate their surroundings. Electronic retinal prosthesis restore useful vision in patients affected by IRDs, and optogenetics is an alternative therapeutic. A major limitation of microbial opsins for restoration of retinal light sensitivity is the high light intensity required for activating channelrhodopsins. A solution to this caveat is the use of opsins with higher light sensitivity but sufficiently fast kinetics for useful motion vision.
We propose a novel approach to restore vision to patients using a virus to express a light sensitive
protein in specific, second-order retina neurons to make them light sensitive. Our approach uses a common
neuronal receptor, modified to add a light receptive function to the remaining light-insensitive retinal
neurons that survive after photoreceptor degeneration. The receptor uses either retinal, which is available
in the eye, or a synthetic chemical photoswitch delivered by intravitreal injection. In this way, the cells in
which the receptor is located respond to light with a change in neural firing. This compensates for their loss
of input from photoreceptors, restoring light responsiveness to the retina and sending information to the
brain to restore vision. In most cases, this approach is independent of the mutation that caused the
photoreceptor degeneration. Exceptions to this approach may be diseases that cause RPE cell death, such
as choroideremia.
To date, versions of this approach, developed by Co-PIs Isacoff and Flannery, and others in the
field, have employed receptors that are rather insensitive to light or very slow in response and so could not
support normal vision. We now propose a new strategy that uses the natural amplification properties of
GPCR signaling to increase sensitivity (by 1000 times) and speed. GPCR signaling cascades are intrinsic
to rods and cones, as well as bipolar, ganglion cells and other cells in the retina. We also pursue a new
discovery, emerging from our preliminary experiments, which enables a combinatorial approach that uses
more than one optical sensor molecule at a time in order to recreate the natural diversity of natural
signaling in the retina that had earlier been missing. Finally, we employ sophisticated behavioral analysis to
test not only the restoration of the ability to tell light from dark or flashing from steady light, but to determine
if the animal is able to see images. Success of this program would represent a major step in the creation of
a retinal prosthetic based on gene therapy.

## Key facts

- **NIH application ID:** 10247536
- **Project number:** 5R01EY028240-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** John Gerard Flannery
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,725
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247536

## Citation

> US National Institutes of Health, RePORTER application 10247536, Optogenetic Vision Restoration (5R01EY028240-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247536. Licensed CC0.

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