# Modulation of Exosome Release for Functional Restoration in Age-related Retinal Disorders

> **NIH NIH P20** · MC LAUGHLIN RESEARCH INSTITUTE · 2024 · $360,000

## Abstract

Project II: Summary
Age-related Macular Degeneration (AMD) is the leading cause of vision loss among older Americans and is
caused by dysfunction of the Retinal Pigmented Epithelium (RPE) leading to neurodegeneration. The RPE
functions to maintain the outer blood-retinal barrier and support photoreceptor function, including regeneration
of visual pigment and turnover of outer segments. Given that a major function of the RPE is to process photo-
receptor outer segments, the proper functioning of the RPE endosomal pathway is important for retinal health.
Thus, RPE-derived exosomes are a likely source of real-time biological information into retinal health and are
available in the systemic circulation. The underlying hypothesis of this project is that release of exosomes (nano-
sized extracellular vesicles) from stressed RPE cells plays a central role in desmosome disassembly, outer
blood-retina barrier (oBRB) integrity, and contributes to pathognomonic deposit formation in AMD. To explore
this hypothesis, I present two aims focused on neurodegeneration and the RPE with the goal of translation of
this work to novel therapeutic interventions in retinal degenerative diseases: Aim 1 interrogates the role of
exosome release in vitro in stressed RPE models of AMD and Aim 2 interrogates the role of exosome release in
AMD and retinal degeneration mouse models. By evaluating complementary in vitro and in vivo AMD models,
our approach is to determine the role of exosome secretion on RPE health, and test whether pharmacological
or gene therapy interventions are possible by: (1) Characterizing the desmosomal and hemidesmosomal content
of basal-side exosomes in aged RPE and RPE stressed by pathophysiological conditions implicated in AMD,
while modulating exosome release, and (2) modulating the level of exosome release in two different and
complementary mouse models of AMD features to identify novel approaches to therapy and/or intervention. This
project is innovative as it tests the novel hypothesis that exosomes from the basolateral side of stressed RPE
cells play a central role in disassembly of desmosomes which impacts oBRB integrity, and contribute to
pathognomonic deposit formation in AMD. Moreover, the proposal is both significant and innovative as it explores
possible avenues for therapeutic intervention aimed at regulating exosome release from RPE, a novel avenue
for AMD treatment to achieve functional restoration in situ. The project is also significant in leveraging my
background in developing and characterizing AMD mouse models, and my expertise in RPE cell biology and
exosome biology. The project plan lays the foundation for my future research program.

## Key facts

- **NIH application ID:** 10771506
- **Project number:** 1P20GM152335-01
- **Recipient organization:** MC LAUGHLIN RESEARCH INSTITUTE
- **Principal Investigator:** Mikael Klingeborn
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $360,000
- **Award type:** 1
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10771506

## Citation

> US National Institutes of Health, RePORTER application 10771506, Modulation of Exosome Release for Functional Restoration in Age-related Retinal Disorders (1P20GM152335-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10771506. Licensed CC0.

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