# Uncovering the molecular identity of retinal cell types, and their responses to nerve injury using single-cell transcriptomics

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $241,530

## Abstract

ABSTRACT
Neurons of the central nervous system (CNS) have been historically categorized into discrete "types" based on
structure, physiological responses, connectivity patterns, and molecular profiles. Heterogeneity can have other
consequences- e.g. recent studies have found that some neuronal types in the retina are more resilient than
other types to optic nerve injury, an event that leads to irrecoverable damage in vision.
My project combines cutting-edge single-cell genomic technologies, advanced computational data analysis and
molecular tools to define heterogeneity of neuronal types comprehensively, to connect molecular definitions to
histology, and explore the functional consequences of this heterogeneity during nerve injury. I will focus on a
tractable system, the mouse retina, which communicates visual responses to the brain. It is as complex as any
other region of the brain (containing ~120 neuronal types), but benefits from having a compact, accessible
structure, and experimental tools make it especially suited for detailed analyses. Building on my previous
postdoctoral work, this project will,
1) Complete the census of the mouse retina, which will the first for any CNS region, by inferring molecular
taxonomies of two of its most heterogenous classes (amacrines and ganglion cells) from data collected using
high-throughput single-cell RNA-sequencing. Using the mouse census, initiate a similar mapping of the
macaque retina, which is harder to access experimentally, but shares important features with humans that are
absent in mice.
2) Conduct a systematic investigation of cell-type specific responses in the retina to optic nerve injury. This
usually leads to a rapid, stereotypic death of retinal ganglion cells (RGCs), but a recent study by my colleagues
reported that some RGC types are more resilient than others. Here, using 1) as a resource, I will identify
factors, cell intrinsic and extrinsic, that make these RGC types resilient.
3) Selective resilience of cell types is now recognized as a feature of diseases like glaucoma and stroke.
Therapies therefore need to cater to different cell types. To learn more, and derive general principles, I will
examine the impact of known therapeutic interventions on the survival of different RGC types, and the
underlying molecular responses, within the optic nerve injury model.
Taken together, my project will derive substantial molecular information underlying neuronal heterogeneity in
the mouse and macaque retina and general principles for cell-type selective resilience following CNS injury in
mice. The lessons from this work will provide valuable guidance for similar studies in less accessible regions of
the brain (e.g. cerebral cortex).

## Key facts

- **NIH application ID:** 10132331
- **Project number:** 5R00EY028625-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Karthik Shekhar
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,530
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132331

## Citation

> US National Institutes of Health, RePORTER application 10132331, Uncovering the molecular identity of retinal cell types, and their responses to nerve injury using single-cell transcriptomics (5R00EY028625-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10132331. Licensed CC0.

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