# Retrograde Signaling by Intrinsically Photosensitive Retinal Ganglion Cells

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $312,000

## Abstract

Classically, photic information was assumed to flow only from rod and cone photoreceptors through bipolar,
horizontal and amacrine interneurons to retinal ganglion cells (RGCs), which were assumed to signal only to
higher visual centers of the brain. Unexpectedly, the PI and colleagues discovered that a subset of RGCs,
namely intrinsically photosensitive retinal ganglion cells (ipRGCs), transmit light-evoked responses
intraretinally to several types of amacrine cells (ACs). The functional significance of this counterintuitive
retrograde signaling is largely unknown. Since ACs are well-known to regulate the physiology of all classes of
retinal neurons, the central hypothesis for this project is that retrograde ipRGC signaling serves to regulate
visual processing in the retina, ultimately shaping vision. In the previous funding period the PI’s team identified
gap junction (GJ) coupling as one mechanism by which ipRGCs signal to ACs. To begin to assess the roles of
retrograde ipRGC signaling, the team genetically knocked out one type of GJ protein specifically in ipRGCs,
and an optokinetic behavioral assay showed a reduction in the mice’s ability to track moving stripes of high
spatial frequencies or low contrasts. Thus, a functional significance of gap junctional ipRGC-to-AC signaling is
that it improves spatial acuity and contrast sensitivity at the behavioral level. The proposed project will test
three hypothesized mechanisms by which gap junctional ipRGC-to-AC signaling could enhance acuity and
contrast sensitivity. Aim 1 will test the hypothesis that gap junctional ipRGC-to-AC signaling potentiates retinal
light responses. The PI’s team will use field-potential recording of bipolar cells and recording of individual
RGCs to measure how these cells’ responses to single light pulses are altered when GJ-mediated ipRGC-to-AC signaling is manipulated. Aim 2 will test the hypothesis that gap junctional ipRGC-to-AC signaling improves
the ability of retinal cells to resolve repetitive changes in light intensity. The team will determine whether
manipulating GJ-mediated ipRGC-to-AC signaling alters bipolar and ganglion cells’ responses to flickering
light. Aim 3 will test the hypothesis that gap junctional ipRGC-to-AC signaling modulates the receptive field
properties of RGCs. The team will test whether manipulating GJ-mediated ipRGC-to-AC signaling alters the
sizes of RGC receptive fields and the strength of center/surround antagonism in these receptive fields. The
research team has strong preliminary data in support of each Aim. The impact of this study will be to: 1)
illuminate the roles of a previously overlooked but functionally important retinal signaling pathway; 2) further
the appreciation of ipRGCs’ contribution to image-forming vision, besides their well-known roles in nonimage-forming photoresponses such as the pupil reflex and circadian photoentrainment; and 3) elucidate the
functions of GJ coupling between amacrine and ganglion cells, which r...

## Key facts

- **NIH application ID:** 9885119
- **Project number:** 2R01EY023660-06A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** KWOON Y. WONG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $312,000
- **Award type:** 2
- **Project period:** 2013-08-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9885119

## Citation

> US National Institutes of Health, RePORTER application 9885119, Retrograde Signaling by Intrinsically Photosensitive Retinal Ganglion Cells (2R01EY023660-06A1). Retrieved via AI Analytics 2026-07-28 from https://api.ai-analytics.org/grant/nih/9885119. Licensed CC0.

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