# Photoreceptor dysfunction associated with rhodopsin mislocalization

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $384,361

## Abstract

Title: Photoreceptor dysfunction associated with rhodopsin mislocalization
Abstract:
Rhodopsin mislocalization is observed in various blinding disorders including syndromic and
non-syndromic retinitis pigmentosa. In most of these disorders rhodopsin mislocalizes to the
inner segment (IS) plasma membrane (PM). Growing evidence suggests that PM
mislocalization of rhodopsin is the root cause of photoreceptor degeneration, but how such
mislocalization causes rod photoreceptor degeneration remains unknown. In this project, we will
test the hypothesis that mislocalized rhodopsin disrupts PM homeostasis thereby causing
dysfunction and degeneration of rod photoreceptor neurons. In rod photoreceptors, rhodopsin is
synthesized at an extremely high rate and delivered to the base of the outer segments (OSs).
This high rate of synthesis is balanced with a high rate of catabolism. Rhodopsin-containing disk
membranes are shed at the tip of the OSs, engulfed, and digested by the retinal pigment
epithelial (RPE) cells. When rhodopsin mislocalizes, a massive amount of rhodopsin is delivered
to the PM of the ISs, where rhodopsin-containing membranes have no apparent contact with
RPE cells. Nevertheless, we recently found that mislocalized rhodopsin is actively eliminated
from the PM while new rhodopsin molecules are continuously delivered to this structure. The
mechanism of elimination will be the subject of this study (Aim 1). Photoreceptor cells are
terminally differentiated neurons that survive during the entire lifespan of vertebrates, including
humans. Therefore, the contents of photoreceptor cells must be continuously renewed. How this
renewal occurs for the OS structure is well-established, but has not been studied for the IS. We
will address the renewal mechanism of IS PM proteins in rod photoreceptors and investigate the
pathological process of disrupting the IS PM protein homeostasis by massive mistrafficking of
rhodopsin there (Aim 2).

## Key facts

- **NIH application ID:** 10212048
- **Project number:** 7R01EY028884-04
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Yoshikazu Imanishi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,361
- **Award type:** 7
- **Project period:** 2020-07-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212048

## Citation

> US National Institutes of Health, RePORTER application 10212048, Photoreceptor dysfunction associated with rhodopsin mislocalization (7R01EY028884-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10212048. Licensed CC0.

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