July 2022

OPHTHALMOLOGY

UNIFIED CLASSIFICATION OF MOUSE RETINAL GANGLION CELLS USING FUNCTION, MORPHOLOGY AND GENE EXPRESSION

How many retinal ganglion cell (RGC) types are there? New research from Northwestern Medicine Ophthalmology’s Schwartz Lab published this week in Cell Reports suggests that the answer is 42.
 
Gregory W. Schwartz, PhD, the Derrick T. Vail Professor of Ophthalmology, and his team, along with collaborators from University of Chicago, Harvard University and Berkeley University, measured more than 1,800 mouse RGCs to arrive at 42. The complement of RGCs in the mouse retina, and similarly in humans, is much richer than the textbook view of classification into ON vs. OFF, transient vs. sustained, and small vs. large receptive field.
 
RGCs represent diverse and specific features of the visual scene, like orientation, direction of motion, speed, color, contrast and more. This study represents the first large-scale unification in retinal neurobiology of the three different modalities for neuronal classification: function, morphology and gene expression.
 
First, the scientists tested the RGCs in the isolated, dark adapted mouse retina with a battery of light stimuli to measure their light responses. Then, those cells were filled with fluorescent dyes for morphological measurements, or their nuclei were extracted for single-cell RNA sequencing. The dual classification of RGCs across modalities allowed Dr. Schwartz and his team to align functional, morphological and genetic classification schemes that were previously disparate. This work provides a template for similar cross-modal neuronal classification projects in labs throughout the world as part of the frontier in circuit neuroscience.
Images of different RGC types from the Northwestern Medicine Schwartz Lab study.
T​o disseminate the information on RGC typology as broadly as possible, Schwartz and colleagues built an interactive website, rgctypes.org, where you can explore the data and download it for your own research. The website will be kept updated with new data. Dr. Schwartz plans to expand the website to include data on:
  • RGC projections to the brain
  • Comparative results on RGCs from other species, including macaque monkeys
  • Data on functional, morphological, and genetic changes in RGCs in retinal disease
Screenshots from rgctypes.org. (A) Landing page for the HD1 RGC. (B) Table of RGC types. (C) Data download area. (D) Expanded, interactive graph of HD1 RGC light responses.
For a review of the conserved visual computations performed by RGCs across vertebrate species, Dr. Schwartz’s book Retinal Computation, published last year, offers a comprehensive modern view of the field.

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