New Glaucoma Research: Is Acute Glaucoma Actually an Inflammatory Disease?

internal view of an eye with glaucoma

Researchers from the United States and China have demonstrated that (a) acute glaucoma in mice presents as an inflammatory disease and (b) elevated eye pressure causes vision loss by setting in motion an inflammatory response similar to that evoked by bacterial infections.

This research is in its earliest stages and has been conducted only with laboratory mice. Nevertheless, the concept shows great promise for persons with acute glaucoma.

The research, entitled Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1ß production in acute glaucoma (explained below) was published in the July 14, 2014 Early Edition of Proceedings of the National Academy of Sciences. Proceedings, first published in 1915, is the official journal of the United States National Academy of Sciences. It publishes research reports, commentaries, and reviews that span the biological, physical, and social sciences.

The authors are Wei Chi; Fei Li; Hongrui Chen; Yandong Wang; Yingting Zhua; Xuejiao Yang; Jie Zhu; Frances Wu; Hong Ouyang; Jian Ge; Robert N. Weinreb; Kang Zhang; and Yehong Zhuo, who represent the following institutions: Sun Yat-sen University, Guangzhou, China; and the Shiley Eye Center, University of California, San Diego, La Jolla.

About Acute Glaucoma and Inflammation Research

From Acute glaucoma discovered to be an inflammatory disease, via Medical Xpress:

“Our research is the first to show an inflammatory mechanism by which high ocular pressure causes vision loss in acute glaucoma patients,” said co-senior author Kang Zhang, MD, PhD and professor of ophthalmology.

Less than 10 percent of glaucoma patients in America have the closed-angle [i.e., acute] form, but in parts of Asia it accounts for almost half of all cases. The higher prevalence of closed-angle glaucoma in Asians and women is believed to be due to a shallower anterior (frontal) eye chamber.

In the study, researchers showed that a rapid, sustained large increase in eye pressure in mice turns on a gene (TLR4) that activates a protein known as caspase-8. This signaling protein in turn triggers the production of inflammatory proteins that normally help mammals fight microbial infections [i.e., a microorganism, especially a bacterium that causes disease].

“This immune response is a double-edged sword because, while these proteins protect us from infection in a normal situation, they stimulate apoptosis (programmed cell death) in retinal cells in cases of acute glaucoma,” said Zhang.

To further confirm the mechanism linking high eye pressure to retinal damage, researchers showed that they could slow retinal cell death in mice with acute glaucoma by suppressing either the TLR4 gene or caspace-8 protein.

The latter is particularly significant because caspace-8 inhibitors are currently in clinical trials for treating cancer and stroke. “By injecting these inhibitors into the eyes of acute glaucoma patients, it may be possible to evaluate and bring them vision-sparing treatments more quickly,” said co-author Robert N. Weinreb.

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, the most common type of glaucoma, the eye’s drainage canals become blocked, and the fluid accumulation causes pressure to build within the eye. This increasing 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 angle-closure glaucoma, also called “acute” 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 cause an acute glaucoma attack. Symptoms can include sudden eye pain, nausea, headaches, and blurred vision. Acute glaucoma is a true ocular emergency and requires immediate treatment.

In normal-tension glaucoma, also called low-tension/low pressure glaucoma, individuals with the disease experience optic nerve damage and subsequent vision loss, despite having normal intraocular [i.e., within the eye] pressure (IOP).

Most eye care professionals define the range of normal IOP 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

Glaucoma results in peripheral (or side) vision loss initially, and the effect as this field loss progresses is like looking through a tube or into a narrow tunnel. This constricted “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 Study from Proceedings of the National Academy of Sciences

From the study summary and abstract:

Acute glaucoma is a sight-threatening condition characterized by a sudden and substantial rise in intraocular pressure (IOP) and consequent retinal ganglion cell death. [Note: Ganglion cells are a type of nerve cell that is found in the retina.]

Angle closure glaucoma, a common cause of glaucoma in Asia that affects tens of millions of people worldwide, often presents acutely with loss of vision, pain, and high IOP.

Even when medical and surgical treatment is available, acute angle closure glaucoma can cause permanent and irreversible loss of vision. TLR4 signaling has been previously implicated in the pathogenesis [i.e., the mechanisms that cause it] of IOP-induced retinal ganglion cell death, although the underlying mechanisms are largely unknown.

In the present study, we used an acute IOP elevation/glaucoma model to investigate the underlying mechanism of retinal ganglion cell death … This study demonstrates the critical role of caspase-8 in IOP-induced cell death in rodent models of acute glaucoma.

These findings identify a mechanism of retinal ganglion cell death and provide a previously unidentified treatment strategy to preserve vision in acute glaucoma.

VisionAware will provide updates of this glaucoma research as they become available.

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