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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $337,788

## Abstract

TITLE: Theranostics of Photoreceptor-RPE-Choroid Neurovascular Unit in Mouse Models of Eye Diseases
PI: Robert J. Zawadzki, Ph.D.
SUMMARY
Inherited and age-related macular degeneration (AMD) are currently responsible for serious 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 in the choroidal
vasculature, a complex of tightly interdependent tissues in the posterior eye. This project will investigate in
vivo the photoreceptor-RPE-choroid complex in animal models of two macular degenerations, RPE
mitochondrial dysfunction model and Doyne Honeycomb Retinal Dystrophy. These models recapitulate two
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 imaging
combined with additional functional tests to characterize age-related changes in the structure and function of
cells of the photoreceptor-RPE-choroid neurovascular unit (PRC-NVU). These studies will be performed
longitudinally in cohorts of mice with the genetic defects, and in wild type controls. The studies will test the
hypothesis that the primary defects in RPE-Bruch's membrane cause secondary deterioration of
photoreceptors and choriocapillaris vasculature. The studies include measures of photoreceptor structure
and electrical activity, bleaching and regeneration of the rod visual pigment rhodopsin, mapping of Bruch's
membrane thickness, RPE cell autofluorescence, the redox status of RPE cells, and choriocapillaris vascular
morphology and flow. At the termination of the study, the choroid-RPE from one eye of each mouse will be
imaged with high resolution ex vivo confocal microscopy; 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 in vivo findings. A novel method for delivering drugs to the RPE via near
infrared light-degradable nanoparticles will be used to locally target therapeutic agents to ailing RPE cells, and
spatially resolved imaging will be used to determine if the therapeutic agents slow and stop disease
progression. By combining longitudinal, in vivo imaging and optical nanotherapies, these studies will lay a
foundation for locally targeted drug delivery in human ocular disease.

## Key facts

- **NIH application ID:** 10090599
- **Project number:** 5R01EY026556-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Robert J Zawadzki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $337,788
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10090599

## Citation

> US National Institutes of Health, RePORTER application 10090599, Theranostics of Photoreceptor-RPE-Choroid Neurovascular Unit in Mouse Models of Eye Diseases (5R01EY026556-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10090599. Licensed CC0.

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