# Genetic Modulators of Glaucoma

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $378,431

## Abstract

Glaucoma is the leading cause of irreversible blindness in the world. While elevated intraocular pressure (IOP)
is a major risk factor, damage and death of retinal ganglion cells (RGCs) underlies visual field loss. However, a
thorough understanding of this disease is a major challenge because its genetic basis is heterogeneous and it
represents a family of age-related disorders resulting from intersecting gene-regulated pathophysiologic
networks. We propose to continue to use the BXD (C57BL/6 x DBA/2J) family of recombinant inbred (RI) lines
of mice as a genetic reference panel (GRP) and to combine our work with human genome wide association
studies (GWAS), to uncover and clarify the genetic heterogeneity that underlies optic nerve (ON) damage. We
have had recent success using this combined approach in the regulation of intraocular pressure (IOP). We are
very well positioned to take the next step and apply this approach to define cellular targets of RGC damage
and death. We propose to uncover phenotypic diversities of glaucoma-related ON damage and uncover
common underlying mechanisms that are shared with IOP modulation. Our long-term research goal is to
identify disease mechanisms and develop neuroprotective therapies to preserve retinal health in patients at
risk for glaucoma. Our overall objective is to identify novel gene products and related mechanisms that lead to
glaucomatous endophenotypes using multi-dimensional genetic analyses, cross-species comparisons (mouse,
rat and human) and validation using novel murine glaucoma models. Our central hypothesis is that molecular
processes leading to glaucoma associated-endophenotypes, such as elevated IOP and ON damage, are
shared across species, and that species comparisons can uncover common underlying mechanisms, and
efficient testing of targeted glaucoma therapeutics. In the current investigation, we perform a systematic
analysis of ON damage, and an additional species—rat. We will mine the extensive databases of IOP and ON
damage that we are generating for more than 70 BXD strains across five age cohorts with the goal of defining
new models of glaucoma. An overall strength of this proposal is the combination of cutting-edge systems
genetics methods, species comparisons of glaucoma phenotypes, and a strong interdisciplinary team that
includes investigators with extensive experience in systems genetics, glaucoma, GWAS in human and rats,
and advanced computational methods. To test our hypothesis, we will perform the following thress studies: 1)
Identify the candidate gene on chromosome 12 that modulates ON damage; 2) Determine if modulation of IOP
and/or ON damage is shared across rodent species; and 3) Identify novel spontaneous glaucoma models
through a comprehensive analysis of our enlarged BXD GRP of 100 or more BXD strains. The outcomes of
these studies will define novel genes and molecular networks that underlie glaucoma-associated phenotypes
and also provide unique glaucoma models for futu...

## Key facts

- **NIH application ID:** 9857597
- **Project number:** 5R01EY021200-06
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** MONICA M JABLONSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,431
- **Award type:** 5
- **Project period:** 2011-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857597

## Citation

> US National Institutes of Health, RePORTER application 9857597, Genetic Modulators of Glaucoma (5R01EY021200-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857597. Licensed CC0.

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