# Uncovering the role of Ankyrins in photoreceptor wiring

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT
Proper synaptic connectivity between photoreceptors and their respective partners is essential for normal visual
transmission and processing. The inability of photoreceptors to form synaptic connections during development
underlies many vision-related neurodevelopmental disorders. Thus, elucidating the developmental mechanisms
that mediate appropriate photoreceptor connectivity will provide insights into devising therapeutic approaches to
treat patients with retinal diseases. In the mammalian retina, the different types of photoreceptors synapse
selectively to distinct postsynaptic targets: horizontal cells and bipolar neurons. During development,
photoreceptors first make contacts to horizontal cells (referred to as first synaptic contact) and then to bipolar
neurons (i.e. second synaptic contact). Although the timing and patterns of connections have been well-
described for photoreceptors, little is known about the early molecular events that coordinate the selective wiring
of photoreceptors to their respective targets. In this proposal, we investigate a new role for the cytoskeletal
scaffolding proteins, Ankyrins in mediating the early developmental events involved in photoreceptor
connectivity. In my preliminary data, I found Ankyrin-B (AnkB) and Ankyrin-G (AnkG) to be differentially
expressed in both a spatial and temporal manner in the developing retina. AnkB is highly expressed in horizontal
cells at early time points when the first synaptic connection between photoreceptors and horizontal cells is being
established, whereas AnkG is expressed at later stages in bipolar neurons when the second synaptic connection
is formed. Moreover, my initial data reveals that loss of AnkB and AnkG results in phenotypes consistent with
synaptic connectivity defects between photoreceptors and their synaptic targets. Additionally, I also find that
there are impaired retinal responses in animals with disruption of AnkB and AnkG compared to controls.
Therefore, I hypothesize that Ankyrins are the key molecules that mediate selective wiring of
photoreceptors to their postsynaptic partners during development. To test my hypothesis, I will utilize
mouse transgenics, high-resolution imaging, and functional visual assays to identify the function of Ankyrins in
photoreceptor connectivity. Specifically, the proposed work will uncover the different roles of Ankyrins in the cone
and rod pathway (Aim 1), the developmental mechanism of when Ankyrins are required for synaptic connectivity
(Aim 2), and the cell-type specific requirements of Ankyrins in photoreceptor connectivity (Aim 3). By performing
the proposed experiments, we will elucidate a new role for Ankyrins in mediating synaptic connectivity in the
developing retina. This work will have broad significance as it may reveal new potential targets that can be used
to restore photoreceptor connections in patients suffering from vision loss.

## Key facts

- **NIH application ID:** 10998599
- **Project number:** 1F31EY035931-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ross Michael Perez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-07-18 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998599

## Citation

> US National Institutes of Health, RePORTER application 10998599, Uncovering the role of Ankyrins in photoreceptor wiring (1F31EY035931-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10998599. Licensed CC0.

---

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