# Transcriptional signatures of glaucomatous retinal and optic nerve head cells

> **NIH NIH K99** · BOSTON CHILDREN'S HOSPITAL · 2022 · $118,611

## Abstract

Project Summary
Glaucoma is one of the leading causes of irreversible blindness in the US and worldwide. The loss of retinal
ganglion cells (RGCs) — neurons that convey visual information to the brain — is a hallmark of glaucoma.
Elevated intraocular pressure (IOP) is a major risk factor for most types of glaucoma, and lowering it remains
the only effective treatment for slowing vision loss. However, many patients with seemingly controlled IOP still
experience progressive loss of vision, underscoring the unmet need for neuroprotective therapies that could
keep RGCs alive, either alone or in combination with IOP-lowering drugs. A critical obstacle toward developing
neuroprotective therapeutics is the lack of true mechanistic understanding of RGC death, neuroprotection, and
survival. Animal models of glaucoma fail to capture some features of the human glaucoma, including the gradual
progression of vision loss and remodeling of the connective tissues of optic nerve head (ONH). Thus, there is a
critical need to directly investigate the mechanisms that underlie death of RGCs in human glaucoma. This
proposal aims to uncover such molecular mechanisms though direct analysis of postmortem human retinas. The
transcriptional profile of macular and peripheral RGCs, and all cells residing at the ONH will be obtained from
genetically and clinically defined human donors (healthy controls and glaucoma patients) using high-throughput
single nucleus RNA sequencing. The transcriptional signatures of glaucomatous RGCs and ONH cells will be
cross compared with that of a multiple mouse models of glaucoma. We expect this to significantly improve our
understanding of the molecular basis of glaucoma and uncover novel genetic targets for the development of
neuroprotective therapies. Furthermore, this proposal details a career development plan for the principal
investigator of the proposed study to build a strong and sustainable research program in an academic research
institute as an independent investigator. The mentored phase of this award will be supervised by a
multidisciplinary advisory team specialized in retinal neurobiology, computational biology, neuro-glia
communication, and glaucoma. The proposed research and training plans will take place in the Center for Brain
Science at Harvard University and the F.M. Kirby Neurobiology Center at Boston Children's Hospital.

## Key facts

- **NIH application ID:** 10524883
- **Project number:** 1K99EY033457-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Aboozar Monavarfeshani
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $118,611
- **Award type:** 1
- **Project period:** 2022-09-30 → 2023-07-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524883

## Citation

> US National Institutes of Health, RePORTER application 10524883, Transcriptional signatures of glaucomatous retinal and optic nerve head cells (1K99EY033457-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10524883. Licensed CC0.

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