# Optoretinography: All-optical measures of functional activity in the human retina

> **NIH NIH U01** · UNIVERSITY OF WASHINGTON · 2022 · $999,362

## Abstract

Project Summary/Abstract
The last few decades have seen major inroads into detailing the physiological mechanisms supporting vision
as well as therapies aimed at rescue and repair of neurons affected by retinal diseases. For the continued
evolution of treatments and their rapid translation to the clinic, it is essential to find a non-invasive, all-optical
biomarker to monitor the efficacy of disease and potential therapeutic agents. To this end, we propose to
develop the optoretinogram, or ORG, the optical analog to the electroretinogram (ERG) which is the current
gold standard for retinal function assessment in humans. The ORG is rooted in classical interferometry and
enables a highly sensitive assay of how neurons interact with light. Using this technique, our group has
demonstrated the ability to visualize light-driven neural activity across a range of spatiotemporal resolution –
from single cells to a collection of neurons, and from µsecs to ms timescales. Here, we aim to expand the
capabilities of the ORG and demonstrate its efficacy for basic science and clinical applications. The proposed
technology is built upon a solid foundation of established approaches, and combines them in new and
complementary ways to achieve an optimal combination of speed, resolution and sensitivity geared towards
overcoming the key challenges faced with imaging cellular structure-function in humans. The core technologies
are phase-resolved OCT, an eye-safe, interferometric method to measure nm-scale changes at ms time
scales in vivo, adaptive optics (AO) to overcome ocular aberrations, increase the signal-to-noise and allow
resolution down to single cells and real-time eye tracking to overcome eye motion and allow targeting,
recording and averaging of responses from single and a collection of retinal neurons. These are implemented
across three ORG platforms. At the University of Washington, we will refine the line-scan phase-resolved OCT
with improvements in optical design and eye-tracking and use it to characterize the basic properties of
phototransduction and inner retinal function in healthy human volunteers and patients with retinal
degenerations. At Stanford University, we will develop a similar line-scan system for rodents, and together with
transgenic models and pharmacology, determine the biophysical mechanisms that underlie the ORG and
develop templates for human recordings. At UC Berkeley, we will push the envelope of speed and sensitivity
by incorporating a real-time eye-tracking system to drive an AO-OCT interferometric probe, with the aim to
measure the tiniest and briefest neuronal changes in the human retina. This bioengineering research
partnership will benefit from complementary expertise, research direction and ORG implementation across the
three sites, and the use of common approaches for image/data analysis, eye tracking and visual stimulation.
Ultimately, the aggregate technology will facilitate a deeper mechanistic understanding of early vis...

## Key facts

- **NIH application ID:** 10486129
- **Project number:** 5U01EY032055-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** DANIEL V PALANKER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $999,362
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10486129

## Citation

> US National Institutes of Health, RePORTER application 10486129, Optoretinography: All-optical measures of functional activity in the human retina (5U01EY032055-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10486129. Licensed CC0.

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