# Functional imaging of retinal photoreceptors

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $427,391

## Abstract

Project summary: This is a R01 renewal to develop functional intrinsic optical signal (IOS) imaging for
physiological assessment of retinal photoreceptors. Retinal photoreceptors are known as the primary target of
both age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Early detection of eye diseases
and objective assessment of therapeutic outcomes are essential steps to prevent vision loss and blindness.
Structural only biomarkers cannot provide enough information for evaluating physiological condition of retinal
photoreceptors, and combined functional test is frequently required for disease detection and treatment
assessment. However, it is time-consuming and costly inefficient to conduct separate structural and functional
measurements. Functional IOS imaging, also termed as optoretinography (ORG) or optophysiology, is based on
near infrared (NIR) light mapping of stimulus-evoked physiological activities in the retina. Because IOS imaging
is based on dynamic processing of retinal images, it can naturally provide structural information offered in
traditional fundus photography. During the first grant period, we have demonstrated stimulus evoked IOS
response at the outer segment of retinal photoreceptors. The fast photoreceptor-IOS occurs immediately after
the onset of the retinal stimulation, differentiating itself from timely delayed IOS changes at the inner retina. The
fast photoreceptor-IOS provides a unique marker for objective ORG of photoreceptor physiology, without signal
contamination of post-photoreceptor layers. We propose here to characterize biophysical mechanism of the fast
photoreceptor-IOS (aim 1); and validate fast photoreceptor-IOS imaging for objective ORG of photoreceptor
function in human subjects (aim 2). The first aim is to use animal models to verify the correlation of the fast
photoreceptor-IOS to the activation phase of phototransduction. A custom-designed hybrid confocal-OCT
ophthalmoscope will be used for in vivo characterization of fast photoreceptor-IOS in WT and rd10 mice. In vitro
time-lapse light microscopy will be conducted to characterize transient outer segment response in individual
photoreceptors. Comparative electron microscopy of dark- and light-adapted retinal tissues will be implemented
to verify light-driven outer segment shrinkage at sub-disc level. The second aim is to verify the feasibility of
clinical translation of using fast photoreceptor-IOS imaging for in vivo ORG of human photoreceptors. We have
recently demonstrated virtually structured detection (VSD) based super-resolution imaging of individual rods and
cones in awake human. During this project, the VSD based super-resolution ophthalmoscopy will be refined to
achieve µm level spatial-resolution and ms level temporal-resolution for imaging fast photoreceptor-IOS changes
in human photoreceptors. Success of this study will pave the way towards pursuing clinical application of
objective ORG of retinal photoreceptors, enabling e...

## Key facts

- **NIH application ID:** 10427264
- **Project number:** 5R01EY023522-07
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** XINCHENG YAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $427,391
- **Award type:** 5
- **Project period:** 2014-04-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427264

## Citation

> US National Institutes of Health, RePORTER application 10427264, Functional imaging of retinal photoreceptors (5R01EY023522-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427264. Licensed CC0.

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