# Molecular Basis of Photoreceptor Wiring

> **NIH NIH R01** · SCRIPPS FLORIDA · 2021 · $101,552

## Abstract

PROJECT SUMMARY
 Mammalian rod and cone photoreceptors are indispensible for vision. They convert light into electrical
response, which is then propagated across the retina circuit and into the brain. Transmission of the electrical
signal generated by the photoreceptors requires their synaptic connectivity with the downstream interneurons,
the bipolar cells. Deficits in synaptic communication between photoreceptors and bipolar cells are known to
cause congenital stationary blindness in humans, a condition characterized by poor light sensitivity and
frequent co-morbidity with many other ocular conditions. Our long-term goal is to elucidate molecular and
cellular mechanisms by which photoreceptors establish synapses and transmit their signals with the hope to
better understand blinding conditions and devising strategies for their treatment.
 Two types of the photoreceptors, rods and cones, form distinct connections with different types of the
bipolar cells. This synaptic specificity segregates visual inputs and plays an essential role in setting up the
fundamental properties of our vision, including a wide dynamic range of light sensitivity and contrast
discrimination. However, the molecular mechanisms responsible for selective connectivity between
photoreceptors and their downstream bipolar neurons are unknown. We have identified a new cell adhesion-
like molecule ELFN1 that specifically present at the photoreceptors synapses. We found that ELFN1 forms a
trans-synaptic interaction with the principal neurotransmitter receptor in bipolar cells, mGluR6. Disruption of
ELFN1 results in selective loss of rod synapses. We hypothesize that ELFN1-mGluR6 interaction play key
roles in mediating selective synaptic connectivity of rod photoreceptors and direct the propagation of light
signal across retina circuit.
 This hypothesis will be tested by pursuing three complementary Specific Aims that will (i) use
knockout mouse models, and genetic rescue experiments to determine cellular mechanisms of ELFN1 function
in the formation of synapse between rod photoreceptors and ON-RBC, (ii) investigate the role of ELFN1 in
directing the propagation light signal across retina circuitry, and (iii) examine molecular mechanisms by which
ELFN1 enables its synaptogenic effects. The strategy proposed to address these aims will entail a synergistic
combination of biochemical, molecular biological, electrophysiological, and physiological approaches, each
exploiting the existence of a powerful array of reagents and animal models.

## Key facts

- **NIH application ID:** 10412170
- **Project number:** 3R01EY028033-05S1
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Kirill A. Martemyanov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $101,552
- **Award type:** 3
- **Project period:** 2017-05-01 → 2022-04-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412170

## Citation

> US National Institutes of Health, RePORTER application 10412170, Molecular Basis of Photoreceptor Wiring (3R01EY028033-05S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10412170. Licensed CC0.

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