Is It Possible to Prevent the Inflammation that Triggers Dry Macular Degeneration? New Research Says Maybe

a retinal photograph of dry AMD
A retina with dry AMD

One of the most significant challenges facing eye and vision researchers is developing an effective treatment for dry age-related macular degeneration (AMD). Although there are now a number of well-regarded FDA-approved drug treatments for wet AMD, the key to effective dry AMD treatment remains elusive, although several potential treatments have emerged in recent years.

Current treatments for dry AMD include a number of non-drug-related measures, including (a) nutritional supplements recommended by the Age-Related Eye Disease Study 2 (AREDS2), and (b) controlling a range of lifestyle factors, including diet, weight, blood pressure, smoking, and blue and ultraviolet light exposure.

Most recently, researchers from the United States and Japan have discovered a “critical trigger”—an enzyme called cGAS, explained below—which starts the inflammation that damages cells and leads to dry AMD and geographic atrophy. Their hope is that this finding will halt inflammation early on in the course of the disease and prevent the progression to vision loss.

Please note that this research is in its very earliest stages and has been conducted thus far only with laboratory mice and human tissue samples. The researchers expect that the development of a drug to stop the cGAS enzyme will take several years. The drug would then have to go through extensive testing to determine its safety and effectiveness. Nevertheless, this research shows promise for developing treatments to prevent inflammation and its progression to dry AMD.

About Enzymes and Dry Age-Related Macular Degeneration (AMD)

This new AMD research has been published in the November 29, 2017 edition of Nature Medicine. Nature Publishing Group (NPG) is a publisher of scientific and medical information in print and online. NPG publishes a range of journals across the life, physical, chemical, and applied sciences and clinical medicine. Topics include current affairs, science funding, scientific ethics, and research breakthroughs.

The authors and researchers represent the following institutions from the United States and Japan: Icahn School of Medicine at Mount Sinai, NY; Texas A&M University; University of California Los Angeles; University of California Irvine; University of Kentucky, Lexington; University of Massachusetts Medical School; University of Virginia School of Medicine; Doheny Eye Institute, Los Angeles; Nagoya University Graduate School of Medicine; Kobe University Graduate School of Medicine; Wakayama Medical University; and University of Tsukuba, Japan.

Some Terminology Related to the Research

Geographic atrophy (GA) is the most severe and advanced form of dry AMD. GA involves patches of cells in the retina that have degenerated or died off:

  • Atrophy: Degeneration of the deepest cells of the retina, called the retinal pigment epithelium (RPE).
  • Geographic: The shape of the atrophied portion of the retina, which resembles the irregular outline of a land mass (geography).
  • The RPE helps to maintain the health of the retinal photoreceptor cells, called rods and cones. These cells are triggered by light to set off a series of electrical and chemical reactions that helps the brain to interpret what the eye sees.
  • The degeneration of the RPE cells also leads to the death of the rods and cones.
  • At present, there is no medical or surgical treatment for geographic atrophy.

Other helpful terms include:

  • Enzyme: A protein that stimulates chemical reactions within the body.
  • DNA: The hereditary material in humans and almost all other organisms. It contains the genetic code that determines all characteristics of a living organism.
  • cGAS: An enzyme that is a component of the immune system. It stimulates the body’s immune response to infections by detecting the presence of foreign DNA and triggering inflammation in response to it.

About Dry Macular Degeneration

The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. “Atrophy” refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula – the small sensitive area in the center of the retina that provides clear central vision – causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

More About the Research

Edited and excerpted from UVA Discovers Trigger for Macular Degeneration That Robs Millions of Vision, via University of Virginia (UVA) Today:

[R]esearchers at the University of Virginia School of Medicine have discovered a critical trigger for the damaging inflammation that ultimately robs millions of their sight. The finding may allow doctors to halt the inflammation early on, potentially saving patients from blindness.

“Almost 200 million people in the world have macular degeneration. If macular degeneration were a country, it would be the eighth-most-populated nation in the world. That’s how large a problem this is,” [they] said. “For the first time, we know in macular degeneration what is one of the very first events that triggers the system to get alarmed and start … hyperventilating. This overdrive of inflammation is what ultimately damages cells, and so, potentially, we have a way of interfering very early in the process.”

[The researchers] determined that the culprit is an enzyme called cGAS. The enzyme plays an important role in the body’s immune response to infections by detecting foreign DNA. But the molecule’s newly identified role in the “dry” form of age-related macular degeneration – which involves no leakage of blood or [fluid] in the eye, and accounts for 85 to 90 percent of all macular degeneration cases – comes as wholly unexpected.

“It’s really surprising that in macular degeneration, which, as far as we know, has nothing to do with viruses or bacteria, that cGAS is activated, and that this alarm system is turned on. This is what leads to the killing of the cells in the retina, and, ultimately, vision loss.”

The researchers noted that … the enzyme may also play important roles in conditions such as diabetes, lupus and obesity, and researchers already are working to create drugs that could inhibit its function.

“Because the target we’re talking about is an enzyme, we could develop [drugs] that could block it,” [they] said. “There are many drugs already on the market that target specific enzymes, such as the statins [which are used to lower cholesterol levels.]”

The researchers also hope to develop a way to detect the levels of the enzyme in patients’ eyes. That would let them determine when best to administer a treatment that blocks cGAS.

“If they have high levels of this enzyme in their eye, they might be a wonderful candidate for this sort of treatment. This is really precision medicine at the single-molecule level.”

VisionAware will continue to report the results of this macular degeneration research as they become available.

Additional Information