# Retinal foveal midget connectivity after acute photoreceptor loss

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $194,375

## Abstract

Project Summary/Abstract
Neuronal cell death due to injury or disease leads to circuit dysfunction and behavioral deficits. In the
visual system, retinal photoreceptor death is a major cause of blindness. Current efforts to restore sight
include replacing lost photoreceptors via stem-cell therapy, transplantation of differentiated neurons and
inducing neuron production from glia. It is evident that designing strategies for successful integration of
‘new’ photoreceptors requires knowledge of the nature, extent and progression of neuronal remodeling
upon photoreceptor loss. Although much has been learned from several non-primate models of injury and
disease, we do not yet know about the circuit rearrangements that occur within the primate fovea, the
region responsible for high acuity and color vision in humans and non-human primates. This project will
fill this significant gap in knowledge by capitalizing on ex vivo fixed Macaque retinal tissue donated by
collaborators at the RIKEN, Japan, in which cone photoreceptors in the fovea were ablated by laser-
photocoagulation. We propose to generate 3D volumes of the tissue samples at ultrastructural resolution
using serial block-face scanning electron microscopy (Aim 1) and reconstruct the foveal midget circuits,
which normally underlie high-acuity vision (Aim 2). We will generate 3D volumes of foveal samples that
received laser-photocoagulation 2 weeks, 2 months or 6 months prior to enucleation. Donated retinal
tissue from unlasered eyes will serve as controls. Comparison of foveal cellular morphology and the
midget connectomes across these samples will provide the first insights into the nature and progression
of remodeling of this critical retinal synaptic pathway over time. Comparison of ON and OFF midget
connectomes will also reveal whether or not there are differences in resilience and plasticity between
these parallel retinal pathways, as discovered in rodent models of injury and disease. In addition to
providing a basic understanding of how the foveal midget circuitry responds to acute cone loss, the EM
volumes will also be a valuable resource for the retinal community for further analyses of the structure
and connectivity of other primate retinal neurons and glia affected by cone loss. Knowledge gained from
this project is an essential step towards halting synaptic miswiring and possibly diverting pathological
changes that could lead to an environment in the primate fovea that is not conducive to circuit repair.

## Key facts

- **NIH application ID:** 10350118
- **Project number:** 1R21EY033447-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Rachel O Wong
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,375
- **Award type:** 1
- **Project period:** 2022-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350118

## Citation

> US National Institutes of Health, RePORTER application 10350118, Retinal foveal midget connectivity after acute photoreceptor loss (1R21EY033447-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10350118. Licensed CC0.

---

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