# RPE, aging and age-related macular degeneration: the role of oxidative stress

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $402,500

## Abstract

Abstract
The most common cause of irreversible blindness in the elderly population in
industrialized countries is age-related macular degeneration (AMD). Degeneration of
retinal pigment epithelium (RPE) cells in association with oxidative stress and
inflammation is a key hallmark of AMD. However, the detailed molecular mechanisms
underlying AMD remain largely unknown and no effective treatment exists for the early
or late atrophic stages of the disease. Oxidative stress affecting the physiological
function and leading to focal loss of the RPE cells has been suggested to be an
important factor contributing to geographic atrophy and vision loss in AMD. Thus
implying that limiting the formation of reactive oxygen species within the RPE may
effectively prevent or reduce RPE dysfunction observed in AMD patients. This proposal
seeks to understand how DJ-1, a multifunctional protein with an antioxidant function,
regulates oxidative stress responses in RPE cells. We have observed increased
amounts of the functional inactive sulfonic oxidized DJ-1 in the RPE of AMD donors as
well as in a mouse model of acute RPE degeneration due to oxidative stress. These
findings provide a solid clinical foundation for pursuing studies on the antioxidant
mechanisms regulated by DJ-1 in RPE cells. Based on our preliminary data we
reasoned of a possible mechanistic pathway via which RPE degeneration results from
overall low levels of native DJ-1 or posttranslational modifications (PTMs) that impair its
function. The three overlapping areas to be investigated in this project are: 1- To test the
hypothesis that RPE degeneration due to oxidative stress is regulated by antioxidant
function of DJ-1; 2- To test the hypothesis that mitochondria dysfunction of the RPE due
to oxidative stress is regulated by DJ-1; 3- To test the therapeutic potential of DJ-1. We
will evaluate the effectiveness of DJ-1 to protect RPE in vivo, in two oxidative stress
relevant pre-clinical mice models: an acute RPE degeneration model and a chronic
model that generates AMD-like lesions in the outer retina. The methods utilized in this
research project include establishment of human and mouse primary RPE cell cultures,
immunoprecipitation, immunostaining, live cell imaging, confocal microscopy, animal
models of RPE degeneration, scanning laser ophthalmoscopy, spectral-domain optical
coherence tomography and electroretinograms.

## Key facts

- **NIH application ID:** 9928931
- **Project number:** 5R01EY027750-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** VERA L BONILHA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928931

## Citation

> US National Institutes of Health, RePORTER application 9928931, RPE, aging and age-related macular degeneration: the role of oxidative stress (5R01EY027750-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9928931. Licensed CC0.

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