# Mechanisms of photoreceptor disc maturation

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $468,079

## Abstract

The experiments described in this proposal address one of the most fascinating unanswered questions in vision
research regarding the molecular mechanisms responsible for photoreceptor outer segment morphogenesis. The
outer segment is a ciliary organelle that produces electrical signals in response to capturing light. A unique
morphological feature of the outer segment is that it is filled with a stack of flattened membrane discs providing vast
surfaces for photon capture and signal amplification. The functional significance of this anatomical arrangement has
been recognized for a very long time, yet our understanding of how discs are built at the molecular level remains
frustratingly rudimentary. This application addresses several poorly understood aspects of photoreceptor disc
morphogenesis, related to the processes of disc expansion, alignment and enclosure. Our preliminary data show
that the edges of newly formed discs contain two distinct types of extracellular links: one connecting discs with the
inner segment plasma membrane and another connecting disc edges between themselves. Experiments described
in Aims 1 and 2 will be devoted to determining the protein composition of each link type and elucidating their
specific roles in supporting the high fidelity of disc elongation and stacking. Aim 3 will focus on the final step in disc
maturation consisting of its scission from the outer segment plasma membrane. We will address whether disc
scission takes place exclusively in rods and explore molecular players involved in this process. Experiments
described in this application will employ versatile molecular tools combined with the state-of-the-art three
dimensional electron microscopy tomographic analysis of the outer segment structure. Addressing these
mechanistic questions is essential for advancing our basic understanding of photoreceptor cell biology, as well as
elucidating the pathophysiological mechanisms underlying inherited blindness frequently associated with defects in
outer segment morphogenesis.

## Key facts

- **NIH application ID:** 10378014
- **Project number:** 5R01EY030451-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Vadim Y Arshavsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $468,079
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378014

## Citation

> US National Institutes of Health, RePORTER application 10378014, Mechanisms of photoreceptor disc maturation (5R01EY030451-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10378014. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*