# Identification of genes involved in photoreceptor recognition and synapse formation

> **NIH NIH R00** · UNIV OF MARYLAND, COLLEGE PARK · 2024 · $246,176

## Abstract

PROJECT SUMMARY/ABSTRACT
 Vision loss caused by the death of photoreceptors is a leading cause of irreversible blindness
worldwide, yet therapeutic options remain limited. For this reason, the NEI's Retinal Disease Program has
identiﬁed the development of strategies for the treatment of retinal degenerations as a core program goal.
Recently, several laboratories have derived photoreceptors from stem cells, making cell-replacement
therapies particularly promising. Additionally, important advances have been made into manipulations that
could stimulate retinal regeneration from the retinal Müller glia. The critical barrier for the success of such
therapies is the integration of derived photoreceptors into existing retinal circuits to reestablish their
function. Yet, we still lack a complete understanding on the mechanisms that underlie the normal wiring of
photoreceptors into retinal circuits, especially for cone photoreceptors.
 Cone photoreceptors of different subtypes are wired into speciﬁc retinal circuits, so that functional
differences (like spectral sensitivity) may be exploited to extract speciﬁc information (like color) from the
visual scene. Our main hypothesis for this proposal is that each cone subtype expresses speciﬁc genes that
allow recognition by its postsynaptic partners (bipolar and horizontal cells), and our main goal is to identify
these genes. To accomplish this, we will ﬁrst generate a complete transcriptomic proﬁling of the four
different cone subtypes in zebraﬁsh, and identify genes that are differentially expressed (aim #1). Based on
this differential expression, we will perform a reverse-genetic screen, where we will assess the functional,
structural and ultrastructural integrity of the cone synapses (aim #2). This will allow us to identify genes that
control the control the formation of synapses between cones and other retinal cells, and that promote the
integration of cones into retinal circuits. We believe that this new knowledge could have direct applications
in the improvement of cell-replacement or regenerative therapies for retinal degenerations. Moreover, wiring
speciﬁcity is a key feature of neural circuits in general. This proposal beneﬁts from the experimental
accessibility of the retina and our deep knowledge of retinal cell types and circuits, but our approach has the
potential to impact the study of other neuronal degenerative diseases.

## Key facts

- **NIH application ID:** 10839398
- **Project number:** 5R00EY030144-03
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Juan Angueyra
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,176
- **Award type:** 5
- **Project period:** 2023-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839398

## Citation

> US National Institutes of Health, RePORTER application 10839398, Identification of genes involved in photoreceptor recognition and synapse formation (5R00EY030144-03). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10839398. Licensed CC0.

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