# Investigating the role of mitochondrial dynamics in retinal pigment epithelium

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $64,926

## Abstract

Project Summary
 The retinal pigment epithelium (RPE) is often the initial site of pathogenesis in many retinal
degenerative diseases. The proposed study aims to understand how mitochondrial dynamics responds to and
affects RPE function and health. The successful completion of the project will provide additional insights into
disease mechanisms. The RPE performs many important functions to ensure photoreceptor homeostasis,
including daily phagocytosis of photoreceptor outer segment. Phagocytosis is a metabolically challenging
process. The formation, transport and degradation of large numbers of phagosomes are energy intensive for
the RPE, as each RPE cell interacts with up to 200 photoreceptor cells. On the other hand, the products of
phagosome degradation could represent an energy source. We therefore speculate that, RPE mitochondria
have to respond and adapt to different daily metabolic events. In many degeneration diseases, impaired
mitochondrial functions have been observed, and this is often associated with defects in mitochondrial
dynamics. However, little is known about mitochondrial dynamics in RPE. In this study, we propose to use
super-resolution high-speed live imaging and electron microscopy to study the dynamics of RPE mitochondria,
including morphology (fission/fusion), distribution and motility. To complement these studies, we will also
conduct metabolic analysis such as Seahorse assay and Fluorescent Lifetime Microcopy to measure
mitochondrial functions. We will focus on answering three questions: 1) How does RPE phagocytosis affect
mitochondrial dynamics? 2) What regulatory machineries drive mitochondrial dynamics? 3) How are RPE
mitochondria dynamics affected in the inherited retinal degeneration, choroideremia? To ensure relevance to
human health and disease, we will compare and contrast our observations in mice with those in human RPE
cell lines, as well as patient-derived iPSC-RPE cultures. By imaging with very high spatial and temporal
resolutions, the study will provide novel insight into RPE mitochondrial dynamics, which in turn will allow us to
uncover new disease mechanism and identify novel therapeutic targets. The scope and potential public health
impact of the proposed study fits well with the missions of NEI to help prevent and treat eye diseases.
 The proposed project also provides invaluable training opportunity for the applicant towards her long-
term career goal to become an independent investigator in molecular and cellular vision research. The
applicant will gain knowledge of the vision system, specifically the interaction between photoreceptors and
RPE. The applicant will also receive training on various cutting-edge microscopy techniques, as well as
patient-derived iPSC as a model to study disease mechanism in vitro. Together with her prior experience in
vascular biology, the training proposed here will set the applicant apart in a uniquely qualified position to study
molecular mechanisms and cell-cell intera...

## Key facts

- **NIH application ID:** 9993155
- **Project number:** 1F32EY031575-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Nan Wu Hultgren
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993155

## Citation

> US National Institutes of Health, RePORTER application 9993155, Investigating the role of mitochondrial dynamics in retinal pigment epithelium (1F32EY031575-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993155. Licensed CC0.

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