# Molecular and functional regeneration of the accessory optic pathway

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $599,812

## Abstract

Project Summary/Abstract
The overall goal of this proposal is to elucidate how to regrow and reconnect injured optic nerves and tracts to
specific target neurons in the brain. Specifically, this proposal investigates mechanisms that promote the
regeneration of connections made by direction selective retinal ganglion cells (DSGC) to their the accessory
optic targets in the brainstem (collectively referred to as the “Accessory Optic System,” or “AOS”). The AOS
serves a crucial role in vision by generating slip-compensating eye movements whenever the head or the eyes
move at slow speeds. In the absence of proper AOS connectivity and function, images appear blurry and
perceptual performance is severely degraded. From a practical standpoint, understanding how to regenerate
the mammalian AOS, and defining the cellular and molecular underpinnings of that regeneration, represent an
ideal model for parsing regeneration of other visual parallel pathways and also mammalian CNS circuits
generally. The AOS is comprised of known retinal neurons and circuits, and the central targets and information
carried in this pathway are rather well understood. Indeed, significant progress has been made by our and
other groups in identifying genetic markers for the DSGCs that drive AOS function and also cellular and
molecular pathways that wire them to their targets. Moreover, both of our laboratories have adopted and
expanded state-of-the-art approaches to measure AOS function at the whole animal level with quantitative
rigor. In parallel to our work, the field of CNS visual system regeneration has reached the crucial milestone of
identifying molecular and activity-based manipulations that allow some retinal ganglion cell (RGC) axons to
regenerate following axotomy. The next crucial milestone is to figure out how to ensure accurate reconnection
of specific RGC types with their correct targets in the brain. Importantly, it remains unclear whether, after
damage to the retina or optic nerve, RGCs and/or their targets re-express, or maintain expression of, the
receptors or ligands that enabled them to correctly wire up with one another during development. It is also
imperative to determine how the specificity of axon-target matching at the level of cell types and targets,
impacts circuit function and behavior. Now that the molecular programs for these developmental steps have
started to become clear, this essential issue relating to optic nerve regeneration can finally be approached with
deep rigor, and we propose here do that in the context of the AOS. The four major aims of this proposal are to:
1) Test the hypothesis that AOS-projecting RGCs are among the cohort of RGC types capable of regenerating
in response to increases in mTOR activation and/or RGC firing.
2) Test the hypothesis that damage to AOS-projecting RGCs and their axons triggers robust changes in axon
guidance receptors and ligands in the relevant RGCs and targets.
3) . Test the hypothesis that re-introduction...

## Key facts

- **NIH application ID:** 9965931
- **Project number:** 5R01EY027713-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Andrew D Huberman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $599,812
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965931

## Citation

> US National Institutes of Health, RePORTER application 9965931, Molecular and functional regeneration of the accessory optic pathway (5R01EY027713-04). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/9965931. Licensed CC0.

---

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