# Neuroprotective Role of Sirt6 in Glaucoma

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $449,924

## Abstract

Project title: Neuroprotective Role of Sirt6 in Glaucoma
SUMMARY
Glaucoma is the second leading cause of irreversible blindness worldwide. It is characterized as progressive
retinal ganglion cell (RGC) death and optic nerve degeneration. Strong risk factors for glaucoma include
elevated intraocular pressure (IOP), age and genetic background. Among them, only IOP is well-studied and
serves as the only treatable target for glaucoma. However, lowering IOP does not always stop the progression
of glaucoma. It is urgent to identify other mechanisms of neuropathy in glaucoma for therapeutic intervention.
Sirtuin (Sirt) 6 is a member of the Sirts that are evolutionarily conserved nicotinamide adenine dinucleotide
(NAD)-dependent histone deacetylases and share homolog with yeast Sir2 protein that critically regulates
lifespan of yeast. It is a histone H3 lysine 9 (H3K9) and H3K56 deacetylase which represses the transcription
activities of several transcription factors involved in aging and inflammation, promotes DNA repair, prevents
genomic instability and maintains glucose homeostasis. These multiple functions of Sirt6 position it as a key
anti-aging molecule. Sirt6 is expressed in the retina but its role in glaucoma is unknown. This application will
integrate a series of novel approaches including our newly developed Sirt6 global and conditional knockout
/overexpression mice, AAV2-mediated gene knockdown, clinic-relevant non-invasive imaging and functional
tests, state-of-the-art imaging to test the hypothesis that Sirt6 plays a key role in the prevention of
dysfunction/degeneration of retinal ganglion cells and their axons in glaucoma. We will: 1) test the
hypothesis that loss of Sirt6 causes pathological changes in the retina and optic nerve resembling glaucoma;
2) test the hypothesis that boosting Sirt6 expression prevents pathological changes in the retina and optic
nerve in IOP elevation-induced glaucoma. Completion of the proposed studies will provide important new
knowledge that may guide the development of novel therapies for glaucoma. This proposal is in line with vision
research priorities identified in the NEI Publication, “Vision Research: Needs, Gaps, & Opportunities”: 1)
Determine the mechanisms by which risk factors, such as age and prior glaucomatous injury, influence
susceptibility of remaining RGC axons to elevated IOP; 2) Apply molecular biology techniques to RGC
neuroscience to dissect factors important for survival, axon regeneration, and physiology; 3) Explore
neuroprotection as an approach for prolonging RGC function and survival.

## Key facts

- **NIH application ID:** 9867317
- **Project number:** 1R01EY031054-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Hua Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $449,924
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867317

## Citation

> US National Institutes of Health, RePORTER application 9867317, Neuroprotective Role of Sirt6 in Glaucoma (1R01EY031054-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9867317. Licensed CC0.

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