# Responses of the Macula to Toxicant Injury: The Role(s) of PGC1α Isoforms in Photoreceptor Neuroprotection

> **NIH NIH K08** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $153,825

## Abstract

PROJECT SUMMARY
The goal of this NIH Mentored Research Career Development Award application is to facilitate the transition of
the candidate into an independent clinician-scientist. Her long-term career goal is to apply her skills in
comparative ophthalmology and molecular genetics to develop novel treatments to address human blindness
caused by the dry form of age-related macular degeneration (AMD), for which there is an unmet therapeutic
need. Her short-term goal in this 4-year K08 program is to train in mechanisms of toxicant-induced pathology
and modelling human exposures in animal models. She will capitalize on the unique environment in and
around NC State University, including the NC State P30 funded Center for Human Health and the Environment
and the close proximity of her laboratory to both Duke University and the National Institute for Environmental
Health Sciences, where mentors and collaborators are located. Key elements of the career development plan
include support from a diverse mentorship committee with expertise relating to all aspects of the proposal,
spanning toxicology, mitochondrial biology, electroretinography and animal models of AMD. The candidate will
participate in didactic training in toxicology, electron microscopy and electroretinography, present at meetings,
publish her work, and ultimately, submit an R01 proposal to the National Eye Institute (NEI).
The candidate’s research project integrates optimally with her career goals and training program. The project
will determine the consequences of exposure of the cigarette smoke toxicant hydroquinone on mitochondrial
density, morphology and function in macular photoreceptors and RPE, and will define the role(s) of different
isoforms of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) on mitochondrial
health in the retina.
Novel animal models will be used that enable study of macular photoreceptors and PGC1α activity. The
specific aims are: 1: To determine whether hydroquinone exposure impairs macular photoreceptor function
and reduces PGC1α and mitochondrial density in a relevant animal model. 2: To determine whether deletion of
specific Pgc1α isoforms leads to development of AMD – like disease in mice and whether this can be
exacerbated by hydroquinone.
This work is expected to yield important insights into why the macula suffers most from dry AMD. The
mechanisms of macular susceptibility are poorly defined, and the study is therefore relevant to the mission of
the NEI. The work will also lead to discovery of novel mediators of retinal mitochondrial health, which may be
candidates as treatments for dry AMD.

## Key facts

- **NIH application ID:** 10374899
- **Project number:** 5K08EY028628-04
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Freya Mowat
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $153,825
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374899

## Citation

> US National Institutes of Health, RePORTER application 10374899, Responses of the Macula to Toxicant Injury: The Role(s) of PGC1α Isoforms in Photoreceptor Neuroprotection (5K08EY028628-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10374899. Licensed CC0.

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