Astrocyte Reactivity in the Glaucomatous Optic Nerve Head: Beneficial or Harmful for Vision?

Daniel Sun, PhD
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary (Harvard) (Boston, MA)
Year Awarded:
2016
Grant Duration:
July 1, 2016 to June 30, 2018
Disease:
Glaucoma
Award Amount:
$150,000
Grant Reference ID:
G2016137
Award Type:
Standard
Award Region:
US Northeastern
Daniel Sun, PhD

Do We Need Optic Nerve Head Astrocytes to Become Reactive in Glaucoma?

Summary

We still don’t know how people lose their vision in glaucoma. To date, we have a strong idea of where in the eye the damage begins, but the biological processes happening at this location, and the cells that are involved, remain unclear. This is important to find out if we want to be able to better target therapeutic interventions. My research focuses on better understanding the role that a type of supporting cell, called astrocytes, plays in the biological process of glaucoma, primarily whether they help to slow down the vision loss in glaucoma or make it worse.

Details

My research focuses on understanding the role that a type of supporting cell called astrocytes play in the biological processes of glaucoma, including whether they help to slow down the vision loss or make it worse. We will use transgenic mice, with specific gene knock-outs, to manipulate the function of these astrocytes and then test the effect this change of function has on cell survival and visual function following experimental glaucoma and an optic nerve crush injury. The results will help to determine whether astrocyte function in glaucoma should be suppressed or promoted and what biological pathways are involved, and having this knowledge could provide new ways of protecting the optic nerve.

There is currently no cure for glaucoma or neuroprotective treatment that directly targets the pathogenic mechanisms in the retina or optic nerve. To improve patient outcome, more treatment options are required. An important step towards alternative treatments is to better understand the pathogenic mechanisms underlying glaucoma. This involves going beyond simply studying the retinal ganglion cells themselves (ie, the cells that undergo damage and death from glaucoma), to understanding the potential role of supporting cells that support the ganglion cells, including astrocytes.

About the Researcher

My path to vision research began as an optometrist graduating from the University of Melbourne, Australia. Although I enjoyed clinical optometry, it was during this time that I found a passion for wanting to understanding retinal diseases, particularly glaucoma. I decided to venture into research and completed my doctoral studies in the area of retinal neurochemistry. I was interested in understanding the selective vulnerability of different retinal cell types and the changes in the circuitry of these cells secondary to retinal ischaemia/reperfusion (ie, loss of blood circulation and its restoration in the eye). Using pharmacologic manipulations, cationic gating experiments, and the electroretinogram, we showed that cone bipolar cells were particular vulnerable to ischaemia/reperfusion injury compared to rod bipolar cells.

In 2007, I transitioned to Boston and began to focus my work on the contribution of optic nerve astrocytes in the pathophysiology of glaucoma. As a postdoctoral fellow at Massachusetts General Hospital, I used a novel transgenic mouse in which individual astrocytes expressed GFP (green fluorescent protein (GFP), which exhibits bright green fluorescence when exposed to light) to define the full morphology and spatial arrangement of astrocytes in the mouse optic nerve head. In this manner I was able to produce an anatomical map of astrocytes within the normal optic nerve head. I then moved to the Massachusetts Eye and Ear Infirmary and as a next step, I studied how these astrocytes reacted and morphologically remodeled when subjected to experimental elevations in intraocular pressure and nerve crush. My current work builds on those most recent findings and now looks into the function or purpose of the astrocyte reactivity and remodeling within the optic nerve head and the mechanisms involved. 

Personal Story

Glaucoma is a very common and yet incurable disease. It is the second leading cause of blindness worldwide, and my family is directly affected by it. It is a complicated disease for which a lot of basic knowledge is still lacking, and an area of research I continue to enjoy working in, ever since I started learning about it as an optometrist. I am very grateful that the BrightFocus Foundation, through the generosity of its donors, is supporting my research and continuing to help make basic science research possible. As an early career scientist, receiving this grant has given me confidence to continue and establish my own independent research.

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