# Theranostics of Photoreceptor-RPE-Choroid Neurovascular Unit in Eye Diseases:

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $594,193

## Abstract

TITLE: Theranostics of Photoreceptor-RPE-Choroid Neurovascular Unit in Eye Diseases
PI: Robert J. Zawadzki, Ph.D.
SUMMARY
Inherited and age-related macular degeneration (AMD) are currently responsible for severe vision impairment
in over 2 million US residents, with prevalence expected to double by 2040 as the population ages.
Degeneration occurs in photoreceptor cells, retinal pigment epithelial (RPE) cells, and the choroidal
vasculature, a complex of tightly interdependent tissues in the posterior eye. This project will continue our in
vivo investigations of morphology and function of the photoreceptor-RPE-choroid complex in animal models of
retinal degenerations, including the RPE mitochondrial dysfunction model and Doyne Honeycomb Retinal
Dystrophy. These models recapitulate major hallmarks of inherited and age-related macular degeneration:
degeneration of RPE cells and age-related increase in extracellular deposits between the RPE and Bruch’s
membrane, which separates the RPE from the choroidal capillary bed. The project will use innovative, cellular-
level resolution in vivo probing of retinal structure and function combined with additional functional tests to
characterize age-related changes in major components of the photoreceptor-RPE-choroid neurovascular unit
(PRC-NVU). These studies will be performed longitudinally in cohorts of mice with genetic defects and wild-
type controls, fed with a high-fat diet (to accelerate disease progression). The studies will test the hypothesis
that primary defects in RPE-Bruch’s membrane cause secondary deterioration of photoreceptors and
choriocapillaris vasculature. The studies include measures of photoreceptor structure and function (using
Temporal Speckle Averaging - Optical Coherence Tomography (TSA-OCT), OCT-based Optoretinography
(ORG)), and full-field Electroretinography (ffERG)), mapping of RPE mosaic and Bruch’s membrane
morphology with water driven transient changes in BrM scattering, RPE cell autofluorescence intensity and
emission spectrum, the redox status of RPE cells, and choriocapillaris vascular morphology using TSA-OCT
Angiography. We will analyze these multidimensional longitudinal data to discover potential structural and
functional biomarkers of PRC-NVU degeneration and evaluate its predictive value for disease progression. At
the termination of in vivo experiments, the choroid-RPE from one eye of each mouse will be imaged with a
custom high-resolution ex vivo confocal microscope equipped with an Optical Coherence Microscopy (OCM)
unit and a LiveCell stage top incubation system allowing imaging of a “live” RPE cells flat-mounted with the
sclera (to allow validation of in vivo observations and evaluation of Fluorescence Lifetime of RPE organelles);
the retina from the second eye of each mouse will be evaluated by conventional histological and biochemical
measurements performed on light or electron microscopes, to allow validation of morphological in vivo findings.
A novel method for...

## Key facts

- **NIH application ID:** 10587983
- **Project number:** 2R01EY026556-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Robert J Zawadzki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $594,193
- **Award type:** 2
- **Project period:** 2017-02-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10587983

## Citation

> US National Institutes of Health, RePORTER application 10587983, Theranostics of Photoreceptor-RPE-Choroid Neurovascular Unit in Eye Diseases: (2R01EY026556-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10587983. Licensed CC0.

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