# Examining the effects of retinal cell loss on downstream visual brain areas

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2022 · $224,070

## Abstract

Because humans rely heavily on vision to experience the world, diseases of the eye are particularly debilitating
in that they have significant adverse effects on patient health and quality of life. Much is known about the
mechanisms underlying retinal cell loss in eye diseases like glaucoma. However, significantly less is known
about how retinal cell loss impacts visual brain areas downstream of the retina. Visual brain areas immediately
downstream of the retina, especially the lateral geniculate nucleus (LGN) of the thalamus and its main cortical
target, primary visual cortex (V1), are likely to undergo substantial structural and functional reorganization
following the removal of their major source of input from the retina. Accordingly, full restoration of visual
perception in patients with eye disease will require “brain-level” vision restoration in addition to repair of the
damaged retina. The goal of this new research program is to fill a glaring knowledge gap by examining the effects
of retinal cell loss on the structure and function of neurons in the LGN. We have developed a model of retinal
ganglion cell (RGC) loss in the ferret through intravitreal injection of kainic acid (KA). Ferrets have a number of
visual specializations homologous to primates, including humans, that make them an excellent model in which
to study the downstream effects of RGC loss. Importantly, the early visual pathways in ferrets are organized into
parallel processing streams enabling examination of differential effects of RGC loss across functionally distinct
neuronal classes in the LGN. As a part of Specific Aim 1, we will characterize the extent, pattern, and possible
RGC-type specificity of cell loss in our ferret model and compare patterns of RGC loss in the ferret with those
observed in human eye disease for phenotypic similarities. Also in Specific Aim 1, we will characterize the impact
of RGC loss on the structure and physiology of LGN neurons. In Specific Aim 2, we will describe the rate of
changes in LGN neuronal structure and physiology after different survival times following KA-induced RGC loss.
We will employ innovative methods such as high-resolution optical coherence tomography imaging, full-field
electroretinogram recording, and retinal histology to quantify RGC loss and to guide multi-electrode array
recordings in the LGN to scotoma locations. We will record simultaneously from multiple individual neurons in
bilateral LGNs downstream of intact and injected eyes in order to quantify physiological response properties and
functional connectivity. Finally, we will utilize brain tissue histological analyses to characterize axonal
degeneration and neuronal morphology in the LGN in order to quantify downstream structural changes.
Quantified structural and physiological data will be correlated per animal to control for variability due to injection
size. Patterns of structural and physiological changes will then be examined across cohorts of animals with
di...

## Key facts

- **NIH application ID:** 10319007
- **Project number:** 5R21EY031052-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Farran Briggs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $224,070
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319007

## Citation

> US National Institutes of Health, RePORTER application 10319007, Examining the effects of retinal cell loss on downstream visual brain areas (5R21EY031052-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10319007. Licensed CC0.

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