# Understanding Photoreceptor Trafficking Pathways to the Outer Segment

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $410,843

## Abstract

ABSTRACT
The first step of vision takes place in the retina where light is captured by the outer segment organelle of
rod and cone photoreceptors. The outer segment is a modified primary cilium that contains a stack of flat
disc-shaped membranes. This structural arrangement maximizes light detection by forcing photons to
pass through hundreds of membrane layers densely packed with the light absorbing protein, opsin. A
byproduct of light absorption is photooxidative damage, which the photoreceptor overcomes by
continuously replacing its entire membrane-rich outer segment with new protein and lipid material.
Defects in outer segment trafficking, formation, and function ultimately result in photoreceptor cell loss
and cause a broad spectrum of inherited retinal dystrophies including retinitis pigmentosa, cone-rod
dystrophy and Stargardt disease. It is now well established that photoreceptors utilize multiple trafficking
pathways to deliver structural and signaling proteins to the light-sensitive outer segment organelle;
however, how these pathways are coordinated, the molecular processes regulating delivery, why a cargo
chooses a specific route remains largely unknown. The goals of our proposal are to investigate the
trafficking pathways of outer segment membrane cargos that reside within the discs (rhodopsin), the disc
rims (peripherin-2 and ABCA4) and the plasma membrane surrounding the discs (CNG channel). This
comprehensive approach will allow us to understand shared and divergent features between specific
trafficking pathways as well as build a complete overview of intracellular routes to the outer segment. Our
aims utilize proximity labeling approaches to uncover transport partners in vivo as well as gene delivery
techniques to rapidly screen candidates for targeting defects and uncover signals governing conventional
and unconventional delivery to the outer segment in mouse rods. Completion of our aims will provide
insight into how outer segment trafficking pathways cooperate to deliver the structural and functional
proteins necessary to form the light-sensing outer segment organelle as well as how these processes fail
during disease. Looking forward, our proposal aims to provide fundamental knowledge about membrane
trafficking to sensory cilia in general as well as help to inform future therapeutic strategies for patients
suffering from inherited blindness.

## Key facts

- **NIH application ID:** 10364187
- **Project number:** 1R01EY032491-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jillian Nydam Pearring
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $410,843
- **Award type:** 1
- **Project period:** 2022-03-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364187

## Citation

> US National Institutes of Health, RePORTER application 10364187, Understanding Photoreceptor Trafficking Pathways to the Outer Segment (1R01EY032491-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364187. Licensed CC0.

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