Is It Possible to Identify and Treat Cell Damage from Glaucoma Much Earlier in the Course of the Disease? New Research Says Maybe

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a view of the retina to check for glaucoma

Glaucoma often is called "the sneak thief of sight" for good reason: Many people are unaware that glaucoma has few symptoms or warning signs in its early stages. Early treatment for glaucoma can sometimes (but not always) slow the progression of the disease. However, as of yet, there is no cure for glaucoma.

Now, researchers from Washington University School of Medicine in St. Louis have identified a biomarker (explained below) that seems to be linked to cell damage in the eye from glaucoma. According to study co-author Rajendra S. Apte, M.D., Ph.D., "We've identified a biomarker that seems to correlate with disease severity in patients, and what that marker is measuring is stress to the cells rather than cell death. Other glaucoma tests are measuring cell death, which is not reversible, but if we can identify when cells are under stress, then there's the potential to save those cells to preserve vision."

Please note that this glaucoma research is in its very earliest stages, has been conducted thus far primarily with laboratory mice, and will require many more years of testing with human subjects. Nevertheless, this concept shows promise for developing future glaucoma treatments to detect optic nerve changes at an earlier stage and initiate treatments much earlier in the disease process.

From the Journal JCI Insight

This new glaucoma research, titled GDF15 (explained below) is elevated in mice following retinal ganglion cell death and in glaucoma patients, has been published in the May 4, 2017 edition of JCI Insight, a new open-source peer-reviewed journal launched by the American Society for Clinical Investigation and the Journal of Clinical Investigation. JCI Insight is dedicated to biomedical research, ranging from preclinical to clinical studies.

The authors are Norimitsu Ban, Carla J. Siegfried, Jonathan B. Lin, Ying-Bo Shui, Julia Sein, Wolfgang Pita-Thomas, Abdoulaye Sene, Andrea Santeford, Mae Gordon, Rachel Lamb, Zhenyu Dong, Shannon C. Kelly, Valeria Cavalli, Jun Yoshino, and Rajendra S. Apte, from Washington University in St. Louis School of Medicine, St. Louis, Missouri.

First, An Explanation of Terms Used in the Research

Here is a brief explanation of some key terms used in this glaucoma research:

  • Biomarker: A substance in the body that can be measured and whose presence indicates disease, infection, or environmental exposure. Biomarkers are measured and evaluated to examine normal body processes, disease processes, or responses to drugs used in a therapeutic intervention.
  • GDF15: Growth differentiation factor 15 (GDF15) is a protein that responds to stress within the body – in this case, the optic nerve. It plays a role in regulating inflammation and cell death in body tissues that are injured by disease.
  • Retinal ganglion cells: Neurons, or nervous system cells. They are located near the inner surface of the retina and give rise to optic nerve fibers that transmit information from the retina to several regions in the brain.

About the Glaucoma Predictor Research

Excerpted from Potential Predictor of Glaucoma Damage Identified, via Newswise:

Studying mice, rats, and fluid removed from the eyes of patients with glaucoma, researchers at Washington University School of Medicine in St. Louis have identified a marker of damage to cells in the eye that potentially could be used to monitor progression of the disease and the effectiveness of treatment.

Glaucoma is the second-leading cause of blindness in the world, affecting more than 60 million people. The disease often begins silently, with peripheral vision loss that occurs so gradually that it can go unnoticed. Over time, central vision becomes affected, which can mean substantial damage already has occurred before any aggressive therapy begins.

Many patients start receiving treatment when their doctors discover they have elevated pressure in the eye. Those treatments, such as eye drops, are aimed at lowering pressure in the eye, but such therapies may not always protect ganglion cells in the retina, which are the cells destroyed in glaucoma, leading to vision loss.

Co-author Rajendra S. Apte says that all current treatments for glaucoma are aimed at lowering pressure in the eye to reduce ganglion cell loss and not necessarily at directly preserving ganglion cells.

Studying mouse models of glaucoma, [the researchers] identified a molecule in the eye called growth differentiation factor 15 (GDF15), noting that the levels of the molecule increased as the animals aged and developed optic nerve damage. When they repeated the experiments in rats, they replicated their results. Further, in patients undergoing eye surgery to treat glaucoma, cataracts and other issues, the researchers found that those with glaucoma also had elevated GDF15 in the fluid of their eyes.

"That was exciting because comparing the fluid from patients without glaucoma to those with glaucoma, the GDF15 biomarker was significantly elevated in the glaucoma patients," Apte said. "We also found that higher levels of the molecule were associated with worse functional outcomes, so this biomarker seems to correlate with disease severity."

A potential limitation of this study is that the fluid samples were taken from the eyes of patients only once, so it was not possible to monitor levels of GDF15 over time. In future studies, it will be important to measure the biomarker at several time points to determine whether levels of the biomarker increase as the disease progresses, Apte said.

What Is Glaucoma?

Glaucoma is a group of eye diseases that can lead to blindness by damaging the optic nerve, which transmits information from the eye to the brain, where it is processed and interpreted. The eye continuously produces a fluid, called the aqueous, that must drain from the eye to maintain healthy eye pressure. Glaucoma is particularly dangerous to your vision because there are usually no noticeable initial symptoms or early warning signs.

The Different Types of Glaucoma

Primary Open Angle Glaucoma

The most common type of glaucoma is Primary Open Angle Glaucoma (POAG). In POAG, the eye's drainage canals become blocked, and the fluid accumulation causes pressure to build within the eye. This pressure can cause damage to the optic nerve, which transmits information from the eye to the brain.

Vision loss is with this type of glaucoma is usually gradual, and often there are no early warning signs. There is a strong genetic predisposition for this type of glaucoma.

Angle Closure Glaucoma

Angle Closure Glaucoma is much less common than POAG in the United States. In this type of glaucoma, the aqueous cannot drain properly because the entrance to the drainage canal is either too narrow or is closed completely. In this case, eye pressure can rise very quickly and can be triggered by pupil dilation.

Symptoms can include sudden eye pain, nausea, headaches, and blurred vision. If you experience these symptoms, you should seek immediate medical treatment.

Normal Tension Glaucoma

In this type of glaucoma, also called low-pressure glaucoma, there is damage to the optic nerve, even though the eye pressure is not elevated excessively. A family history of any type of glaucoma, cardiovascular disease, and Japanese ancestry are a few of the risk factors for this type of glaucoma.

This type of glaucoma is treated much like POAG, but the eye pressure needs to be kept even lower to prevent progression of vision loss.

Secondary Glaucomas

Secondary glaucomas are those that develop as secondary to, or as complications of, other conditions, including eye trauma, cataracts, diabetes, eye surgery, or tumors.

Series of four photos demonstrating typical progression of vision loss due to glaucoma. Source: National Eye Institute

The typical progression of vision loss from glaucoma
Source: National Eye Institute

Detecting Glaucoma

Because glaucoma has no obvious initial symptoms, a comprehensive dilated eye exam is critical to detect early glaucoma changes. People who are over 40 should have a dilated eye examination from an ophthalmologist or optometrist at least every two years. African Americans; people who are over 35 and have a family history of glaucoma; and everyone age 60 or older should schedule a comprehensive eye examination every year.

You can learn more about glaucoma detection and treatment at How Can I Detect Glaucoma if There Are No Initial Symptoms?, What Are the Different Treatments for Glaucoma?, and Tips for Taking Glaucoma (and Other) Eye Drops at VisionAware.

More About the Glaucoma Detection Research from JCI Insight

Here is more information about the study, excerpted from the article Abstract and Introduction, with the full article available online:

Glaucoma is the second leading cause of blindness around the world. It is a group of … diseases characterized by neuroretinal degeneration associated with death of retinal ganglion cells (RGCs), which in turn leads to optic neuropathy. In glaucoma, progressive optic neuropathy, if left untreated, leads to visual field (VF) defects that may ultimately result in irreversible blindness.

Numerous factors — including genetics and race, as well as ocular characteristics such as intraocular pressure (IOP) and central corneal thickness — have been identified as risk factors in the development and progression of glaucoma. Currently, all medical and surgical therapies for glaucoma focus on lowering IOP as a strategy to protect RGCs from cell death.

Although neuroprotection for glaucoma would be highly desirable, therapeutic strategies that have focused on neuroprotection have thus far failed to demonstrate efficacy in clinical trials, with no agents currently approved by regulatory authorities.

Another impediment for effective glaucoma treatment is the paucity of molecular markers that predict progression of glaucomatous neurodegeneration that results in optic neuropathy. Treating physicians have generally relied on VF testing, IOP measurement, and optic nerve monitoring as metrics for assessing whether disease is adequately controlled.

However, the nature of VF testing, lack of precise correlation of IOP with disease risk, and lack of validated normative databases for optic nerve imaging techniques, such as optical coherent tomography (OCT), contribute to the persistent challenges of glaucoma management.

Of significant concern, these evaluations presently form the basis for treatment decisions regarding additional medical and surgical interventions to prevent disease progression and vision loss. Therefore, there is an acute need to identify specific molecular markers that quantify glaucomatous neurodegeneration by accurately and objectively measuring RGC-specific cell death.

In this study, we have, to our knowledge, characterized in mice and rats a novel molecular marker of glaucomatous neurodegeneration. We have further validated our findings in human glaucoma patients with varying degrees of disease severity. These results highlight a protein with potential use as a marker of glaucomatous neurodegeneration.

Additional Glaucoma Information


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