# Defining oxidative stress induced changes in RPE that control RPE and photoreceptor degeneration

> **NIH NIH R00** · UNIVERSITY OF SOUTH FLORIDA · 2021 · $224,250

## Abstract

Summary
Age-related macular degeneration (AMD) causes vision loss among many older individuals, and
the retinal pigment epithelium (RPE) is thought to be a critical site of injury. Vision loss in AMD
occurs due to photoreceptor degeneration and/or choroidal neovascularization. Geographic
atrophy (GA), the advanced form of dry AMD, is characterized by the breakdown of RPE,
choriocapillaris, and photoreceptors, especially in the macula. Lack of clear understanding of the
molecular mechanisms of GA hinders the development of therapy. For lifelong maintenance of
photoreceptors, RPE cells play an essential role in phagocytosis and degradation of tips shed
from photoreceptor outer segments (POS). Photoreceptors and RPE cells are susceptible to injury
from mitochondrial oxidative stress. The central goal of the project is to understand how
photoreceptor degeneration occurs in GA. I hypothesize that oxidative stress impairs
phagocytosis and lysosome function and ultimately activates inflammatory processes in RPE that
stimulate geographic atrophy. I will test my hypothesis in RPE cell culture and in a new mouse
model of age dependent RPE atrophy that was recently developed in our lab. In this model we
used the cre/lox system to generate an RPE-specific deletion of Sod2, the mitochondrial gene for
manganese superoxide dismutase (MnSOD). These mice develop a normal RPE but overtime
the RPE has elevated oxidative stress resulting in phenotypic changes that are commonly
observed in AMD, including RPE injury, loss of function and subsequent retinal degeneration. In
the context of GA, I have following aims: (1) To characterize the impact of oxidative stress on
phagocytosis, lysosomal function and inflammasome activation in RPE; (2) Identify molecular
changes in RPE under oxidative stress. These studies will illuminate signaling pathways that drive
photoreceptor and RPE loss and will provide a foundation to develop new therapeutic targets to
prevent disease progression in AMD.

## Key facts

- **NIH application ID:** 10315588
- **Project number:** 3R00EY027013-04S1
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Manas R Biswal
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $224,250
- **Award type:** 3
- **Project period:** 2016-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315588

## Citation

> US National Institutes of Health, RePORTER application 10315588, Defining oxidative stress induced changes in RPE that control RPE and photoreceptor degeneration (3R00EY027013-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10315588. Licensed CC0.

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