Is Glaucoma a Genetic Disease? Three New Research Projects Pinpoint Six Specific Genes

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photograph of retina with glaucoma

Three new research projects exploring the role of genes – and six genes in particular – as possible causes of glaucoma have been published simultaneously in the August 31, 2014 online edition of Nature Genetics.

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. Although research scientists are the primary audience, news summaries and articles make many of the most important papers understandable to scientists in other fields and the general public. Topics include current affairs, science funding, scientific ethics, and research breakthroughs.

About Genetics and Glaucoma Research

Excerpted from Six gene variations linked to glaucoma risk at ABC Science-Australia:

Scientists have identified six genetic variants associated with the eye condition glaucoma in people from around the world including Australia. The discovery, in three major studies, could help identify people at higher risk of the disease and lead to earlier screening and treatments.

All three studies, published … in Nature Genetics, identify gene sequence variations of the ABCA1 gene, which is involved in the regulation of cellular cholesterol and lipid metabolism, as playing a role in the eye disease.

Professor Jamie Craig, of the South Australian Health and Medical Research Institute and joint leader of the Australian project, says the finding is significant. "It's rock solid that this is an important result because it has been found in three different ways," says Craig, who is also from Flinders University's Centre for Ophthalmology and Eye Vision Research.

"All [three] papers were done in different populations with different strategies and all identified the same gene. It … tells us for sure it is contributing to glaucoma at least partly through intraocular [i.e, within the eye] pressure pathways."

Craig says the findings may in the future be used to develop risk profiles that will allow doctors to know whether a person has high-risk of their glaucoma being severe. "We are looking at ways to add up a genetic risk profile," says Craig. "So if you can say if you've got a larger load of these variant genes, your risk is high."

However, he cautions it will take several years of experiments before the exact role of the genes identified in these studies is known, and these steps need to be taken before new treatment strategies can be planned.

What Is Glaucoma?

The term "glaucoma" describes a group of eye diseases that can lead to blindness by damaging the optic nerve. It is one of the leading causes of vision loss and blindness. The human eye continuously produces a fluid, called the aqueous, that must drain from the eye to maintain healthy eye pressure.

Types of Glaucoma

  • In primary open-angle glaucoma (POAG), the most common type of glaucoma, the eye's drainage canals become blocked, and the resultant 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 usually gradual and often there are no early warning signs.
  • In normal-tension glaucoma, also called low-tension or low-pressure glaucoma, persons with the disease experience optic nerve damage and subsequent vision loss, despite having normal intraocular [i.e., within the eye] pressure (IOP). This type of glaucoma is treated much like POAG, but eye pressure needs to be kept even lower to prevent progression of vision loss.
  • Secondary glaucomas develop as secondary to, or as complications of, other conditions, including cataracts, diabetes, eye trauma, eye surgery, or tumors. In many of these glaucomas, damage to the fluid drainage canal must be addressed with medication or surgery.

Eye Pressure and Glaucoma

Most eye care professionals define the range of normal within-the-eye pressure as between 10 and 21 mm Hg [i.e., millimeters of mercury, which is a pressure measurement]. Most persons with glaucoma have an IOP measurement of greater than 21 mm Hg; persons with normal-tension glaucoma, however, have an IOP measurement within the normal range.

Visual Field Loss from Glaucoma

Glaucoma results in peripheral (or side) vision loss initially, and the effect as this field loss progresses can be like looking through a tube or into a narrow tunnel. This "tunnel vision" effect makes it difficult to walk without bumping into objects that are off to the side, near the head, or at foot level:

A living room viewed through a constricted visual field

A living room viewed through a constricted visual field.
Source: Making Life More Livable. Used with permission.

Glaucoma is an especially dangerous eye condition because most people do not experience any symptoms or early warning signs at the onset. Glaucoma can be treated, but it is not curable. The damage to the optic nerve from glaucoma cannot be reversed.

More about the Research from Nature Genetics

The First Study: Australia and New Zealand

The first study, entitled Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma, examined potential genes involved in primary open-angle glaucoma (POAG).

The study included 1,155 subjects from the Australian and New Zealand Registry of Advanced Glaucoma with severe POAG, and 1,992 control subjects, who did not have the disease. Genetic testing identified variants of three genes that significantly increased the risk for POAG in Australians and Americans of European descent. (Source: ABC Science)

From the Nature Genetics abstract:

Primary open-angle glaucoma is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls… [W]e show that these genes are expressed within the human retina, optic nerve, and trabecular meshwork, and that two of the genes are also expressed in retinal ganglion cells.

[Note: Aqueous fluid drains through a filtering meshwork of spongy tissue along the outer edge of the iris, called the "trabecular meshwork," where the iris and cornea meet, and into a series of tubes, called Schlemm's canal, that drain the fluid out of the eye.]

[Note: In the human eye, a layer of cells in the retina, called photoreceptor cells, detects light and a separate layer of cells, called "ganglion cells," relays that information to the brain.]

The Second Study: Multi-Ancestry

The second study, entitled Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma, examined potential genes associated with high intraocular pressure (IOP) and glaucoma.

This study involved genetic screening of 35,296 subjects from the International Glaucoma Genetics Consortium. The subjects included persons of Asian and European descent from seven countries.

Genetic testing identified four new genes associated with high IOP and glaucoma. One of the genes is the ABO gene, which determines blood group, and higher eye pressure appears to be linked to blood type B. (Source: ABC Science)

From the Nature Genetics abstract:

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium, comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known [locations] for IOP and POAG and identify four new IOP-associated [gene locations].

The Third Study: China and Singapore

The third study, entitled Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma, is the first large-scale study to examine potential genes involved in primary open-angle glaucoma (POAG) in an Asian population.

The study included 1,007 subjects with severe POAG, and 1,009 control subjects who did not have the disease, all from southern China. Genetic testing identified variants near two genes associated with glaucoma risk in people from China and Singapore. (Source: ABC Science)

From the Nature Genetics abstract:

We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. Both the ABCA1 and PMM2 [genes] are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.

Additional Information


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Cultural Diversity
Medical Updates
Glaucoma
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