# HIGH THROUGHPUT SINGLE CELL TRANSCRIPTOMIC APPROACH TO IDENTIFY SUSCEPTIBLE CELL TYPES AND GENE EXPRESSION CHANGES IN HUMAN GLAUCOMA

> **NIH NIH R21** · HARVARD UNIVERSITY · 2021 · $295,750

## Abstract

ABSTRACT
Glaucoma, the leading cause of irreversible blindness worldwide, results from loss of retinal
ganglion cells (RGCs), which carry visual information from the eye to the rest of the brain.
Current treatment strategies center on lowering intraocular pressure (IOP), the only known
modifiable risk factor for glaucoma. However, significant unmet need persists, and a
neuroprotective strategy targeting glaucomatous RGCs directly would offer a powerful
complementary approach. To date, however, no neuroprotective therapies have successfully
entered the clinic. One major obstacle is that little is known about which of many human RGC
types are most susceptible, and what molecular changes occur in RGCs prior to their demise.
This project uses single cell transcriptomic profiling and integrative computational analysis to
address these gaps in our knowledge. Over the past five years, we have helped to develop
methods for high throughput single cell RNA sequencing (scRNA-seq) and applied them to
retina – first in mice, then in non-human primates, and subsequently in humans and in mouse
models of neuronal injury. Most recently, we have implemented the related method of single
nucleus RNA-seq (snRNA-seq) so that we can profile tissue obtained post-mortem, frozen and
banked. We now propose to obtain and analyze single nucleus transcriptomes of RGCs from
well-characterized glaucomatous and normal human retinas. The number of samples must be
large, because glaucoma is a heterogeneous disease with diverse genetic and non-genetic risk
factors. It is therefore important to study diverse groups, so we can determine whether they
converge on common molecular patterns. Specifically, we will profile at least 2000 RGCs from
each of 200 human donor eyes, 150 from individuals with verified glaucoma and 50 from age-,
sex- and race-matched controls. From the data we obtain, we will (a) determine whether specific
RGC types are selectively resilient or vulnerable in glaucoma and (b) identify genes differentially
expressed between glaucomatous and normal RGCs of each type. Finally, we will perform
similar analysis on a high-IOP mouse model of glaucoma, helping us understand the extent to
which diseases processes in humans are accurately modeled in mice. Our results will provide a
powerful resource of sufficient power to transform our view of this prevalent, complex and
incompletely understood blinding disease.

## Key facts

- **NIH application ID:** 10106084
- **Project number:** 1R21EY032219-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** JOSHUA R SANES
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $295,750
- **Award type:** 1
- **Project period:** 2020-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106084

## Citation

> US National Institutes of Health, RePORTER application 10106084, HIGH THROUGHPUT SINGLE CELL TRANSCRIPTOMIC APPROACH TO IDENTIFY SUSCEPTIBLE CELL TYPES AND GENE EXPRESSION CHANGES IN HUMAN GLAUCOMA (1R21EY032219-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10106084. Licensed CC0.

---

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