# Autophagy and Retinal Ganglion Cell Death in Glaucoma

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $475,493

## Abstract

ABSTRACT
Glaucoma is a group of diseases, second leading cause of permanent blindness worldwide, characterized by
the chronic degeneration of RGC axons and progressive loss of retinal ganglion cells (RGCs), which results in
visual field defects and vision loss. Elevated intraocular pressure (IOP) is the best-well known factor contributing
to the onset and progression of glaucoma. There are not therapeutic treatments to offer neuroprotection in
glaucoma. Current glaucoma therapies are directed at lowering IOP, but cannot rescue RGCs. A better
understanding of the exact molecular mechanisms triggering RGC death and axonal degeneration in glaucoma
is essential for the development of neuroprotective treatments.
Autophagy is a lysosomal degradative process, which plays a central role in cellular homeostasis by eliminating
damage organelles and proteins. In addition to having a key role on maintaining cellular and tissue homeostasis,
autophagy is regarded as a survival pathway, involved in stress-induced adaptation. Dysfunction of the
autophagy pathway has been associated to a growing number of human diseases, in particular age-related
diseases, as well as to several neurodegenerative disorders. Paradoxically, in the neural tissue, autophagy plays
an important role in neuroprotection as well as neuronal injury and death depending on the circumstances.
Although not extensively, autophagy within a context of glaucoma, has been investigated by independent
laboratories using different experimental models. While all of the studies agree that autophagy is activated in
RGC in response to injury or elevated IOP, there is no consensus on whether autophagy promotes survival or
triggers cell death. Latest studies seem to suggest that a protective or pro-death role of autophagy depend on
the initial injury (i.e traumatic insult vs IOP elevation). Moreover, autophagy seems to have a different role in
RGC death and axonal degeneration.
The purpose of this grant application is to investigate the independent contribution of autophagy to apoptotic
RGC death and axonal degeneration in acute injury and chronic hypertensive experimental models of glaucoma.
For this, we will use unique tools generated in our laboratory, including our unique DBA/2J transgenic mouse
glaucoma models with upregulated and deficient basal autophagy. We anticipate that completion of this project
will contribute to a further understanding of the role of autophagy in neurodegeneration in glaucoma. Most
importantly, our studies have the potential of identifying a novel therapeutic target for the treatment of ocular
hypertension and glaucoma.

## Key facts

- **NIH application ID:** 10912488
- **Project number:** 5R01EY033600-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Paloma Liton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $475,493
- **Award type:** 5
- **Project period:** 2022-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912488

## Citation

> US National Institutes of Health, RePORTER application 10912488, Autophagy and Retinal Ganglion Cell Death in Glaucoma (5R01EY033600-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10912488. Licensed CC0.

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