Glaucoma: Eye Biology, Nerve Damage, and Recent Research
What Is Glaucoma?
The word “glaucoma” refers to a group of eye problems that involve damage to the optic nerve. This nerve transmits signals from the retina at the back of the eyeball to the vision centre of the brain, which creates an image. In many cases of glaucoma, the pressure inside the eyeball is increased. This injures the optic nerve and causes loss of vision.
Glaucoma can generally be treated once it's discovered. At the moment, however, the optic nerve can't be repaired and any vision that has been lost before the diagnosis can't be restored. The cause of the disorder isn’t completely understood. A better understanding of the disease could lead to improved treatments. Recent research may be very significant in this regard.
The numbers in the eye shown above represent the structures named below. Though Schlemm's canal is one structure, in places it consists of more than one passageway. 1 = sclera, 2 = choroid, 3 = Schlemm's canal, 4 = iris root, 5 = cornea, 6 = iris, 7 = pupil, 8 = anterior chamber, 9 = posterior chamber, 10 = ciliary body, 11 = lens, 12 = vitreous chamber, 13 = retina, 14 = optic nerve, 15 = suspensory ligament
Circulation of Fluid in the Eye
In a healthy eye, a liquid known as aqueous humour is secreted by the ciliary body into the posterior chamber of the eye. This chamber is located between the suspensory ligament and the back of the iris, as shown in the illustration above. The liquid comes from blood plasma. It moves through the pupil (an opening in the middle of the iris) and into the anterior chamber. The anterior chamber is located between the front of the iris and the cornea.
The aqueous humour is an essential liquid for the health and functioning of the eye. It contains nutrients for the eye and removes waste substances and debris. It also help the eye to maintain its shape, which is necessary for effective light transmission.
The aqueous humour drains from the anterior chamber into a spongy, sieve-like tissue known as the trabecular meshwork. The drainage area is located in the angle between the cornea and the iris. The fluid travels from the trabecular meshwork into the Schlemm's canal, then into connector channels, and finally into the bloodstream. Aqueous humour is continually being secreted from the blood and then drained back into it.
One problem with illustrations that show a flat section of the eye is they may give the viewer a false impression. For example, in the two illustrations shown above, it looks as though the "angle" is present at only two places in the eye. In reality, because the iris and the cornea are circular, the angle is, too.
The iris is the coloured part the the eye and is circular. It's covered by the transparent cornea. The sclera is the white part of the eye.
Drainage Problems in the Eye
In many people with glaucoma, the drainage system described above doesn’t work properly. The aqueous humour isn’t drained from the eyes fast enough or is blocked from entering the trabecular meshwork. As a result, the pressure in the area increases. This pressure is transmitted to the vitreous chamber of the eye, which holds a gel known as the vitreous humour. Unlike the aqueous humour, the vitreous humour is a permanent material and isn’t created and drained. The increased pressure in the eye (the intraocular pressure) injures the optic nerve.
Glaucoma generally develops in older people but sometimes appears in younger ones. Some people develop increased pressure in their eyeball without developing glaucoma. Others have glaucoma without increased pressure in their eyeball. These observations add to the mysteries of the disease. The disease is more common in people who have specific disorders, including hypertension (high blood pressure) and diabetes.
Symptoms of glaucoma don't appear until the disease is at an advanced stage. It's important to get eyes checked regularly so that the disease can be recognized at an early stage and vision loss stopped.
Fluid Drainage in the Eye and Glaucoma
Types of Glaucoma
Multiple types of glaucoma exist. The names of the different types sometimes vary, which can cause confusion. The classification system given below is used by John Hopkins Medicine in the United States and the National Health Service in Britain.
Open Angle (or Primary Open Angle)
Open angle glaucoma is by far the most common type of the disease. Its name is derived from the fact that the angle between the cornea and the iris is wide, as it should be. The condition is thought to be caused by the drainage canals being slowly clogged or by death of cells in the drainage area. These factors lead to increased pressure in the eyeball. In some cases, however, the intraocular pressure is normal and the problem is believed to arise due to a different reason. Some organizations classify this variation as normal tension glaucoma.
Angle Closure (or Narrow Angle)
Some people have unusual eye anatomy in which the structures around the drainage area are crowded together. The angle between the cornea and the iris is narrow. This puts a person at risk for angle closure glaucoma. The condition develops suddenly when the iris is pushed over the drainage area by pressure of some kind. Intraocular pressure may then increase rapidly, damaging the optic nerve. Immediate medical attention is essential in order to retain vision.
Secondary glaucoma is produced by another condition. This condition may be an eye injury, a particular medication, a particular type of surgery, or disorders that cause long-term and widespread inflammation.
Childhood (Congenital or Developmental)
Congenital glaucoma is diagnosed in babies and young children up to the age of around three. The condition is present at birth, but its effects may not be noticed immediately. It's caused by a problem in the development of the eye's drainage system. The sooner the disorder is diagnosed and treated, the better the outcome.
An Overview of Glaucoma
Peripheral vision is lost first in glaucoma. Central vision isn't lost until the disease is at a very advanced stage.
Optic Nerve Damage
The retina consists of layers. The rods and cones (R and C in the simplified diagram above) are stimulated when struck by light energy. An electrical signal is then transmitted through the cell layers of the retina and along the optic nerve to the brain.
The retinal ganglion cells (G) are neurons (nerve cells) located at the back of the retina. Their extensions or axons (Ax) travel along the bottom of the retina at about an angle of ninety degrees and eventually form the optic nerve. This leaves the eye in an area known as the optic disc (or the head of the optic nerve), which is labelled in the illustration below. In glaucoma, the retinal ganglion cells and the optic disc are damaged. This means that the electrical signal is hindered in its journey from the rods and cones to the brain.
Vision loss caused by glaucoma can't be reversed, but further damage to eyesight can often be prevented. The goal of most treatments is to reduce the amount of aqueous humour that's made or to help it drain. Treatments generally involve special types of eye drops, oral medications, or surgery. Eye drops and medications may cause side effects. Some types of surgery may cause complications or need to be repeated over time.
Potential Benefit of Lipoxins
Current glaucoma treatments deal with problems within the eye. It would be wonderful to find a treatment that prevents further damage to the optic nerve. Researchers may have discovered a substance that can do this. It should be noted that the research described in the studies mentioned below was performed with rodents. The news is certainly hopeful, but further research involving clinical trials in humans is needed.
Researchers from the University of California, Berkeley and the University of Toronto have discovered that specific lipoxins are anti-inflammatory and neuroprotective in rats and mice. The chemicals are secreted by astrocytes, star-shaped cells located around neurons. (Since we are mammals like rats and mice, we have astrocytes that produce lipoxin, too.) Lipoxins A4 and B4 are the kinds that are beneficial with respect to glaucoma.
According to the researchers, in glaucoma the astrocytes are injured and stop their production of the helpful lipoxins. As a result, the optic nerve is damaged. The scientists found that administering lipoxins to rats and mice with glaucoma stopped the degeneration of retinal ganglion cells. The researchers suspect that the lipoxins will eventually be useful for humans with glaucoma and perhaps for people with other neurodegenerative diseases.
At present, there is no cure for glaucoma, which is estimated to affect 80 million people worldwide.— Yasmin Anwar, News Release from the University of California, Berkeley
Function of Schlemm's Canal
One of the frustrations of dealing with glaucoma is that its cause isn't fully understood. Multiple causes may exist. Researchers at Korea's Center for Vascular Research in the Institute of Basic Science have made some potentially significant discoveries. The scientists' research suggests that problems in the Schlemm's canal may be responsible for some cases of glaucoma.
Like other cells in the body, the endothelial cells in the wall of the Schlemm's canal contain vacuoles, or sacs. Some of the vacuoles in the canal cells are unusually large. They transport aqueous humour across the wall of the canal and towards the bloodstream. They therefore play a vital role in maintaining normal pressure in the eye.
Proteins and a Receptor in Schlemm's Canal
The Korean scientists' research was centred on proteins named angiopoietins. The specific angiopoietins that the researchers investigated are named Ang1 and Ang2. Proteins often bind to receptors on the cell membrane in order to trigger a particular activity. Ang1 and Ang2 bind to a receptor called Tie2. This binding is known to be important in the Schlemm's canal.
Effects of Decreased Tie2
The researchers found that mice with insufficient Tie2 in their eye had a high intraocular pressure, damage to neurons in their retina, and partial loss of vision. In addition, they had a greatly decreased number of large vacuoles in the endothelial cells of their Schlemm's canal, suggesting that they were experiencing problems in draining liquid from their eye.
Observations in Older Mice
The risk of glaucoma in humans increases as people age. Interestingly, the scientists found that compared to younger mice, older ones has a decreased level of large vacuoles, Tie2, Ang1, and Ang2. They also had a lower level of Prox1, another protein involved in the activity of angiopoietin and Tie2.
Angipoietin/Tie2 and Glaucoma
Experimental Treatments in Mice
Yet more evidence supports the idea that the angiopoietin-Tie2 receptor system may be involved in glaucoma, at least in mice. The researchers injected an antibody named ABTAA into one eye of mice but not into the other. ABTTA stands for Ang2-binding and Tie2-activating antibody. One week after the treatment, the eye that had received the antibodies had an increased number and size of large vacuoles in the Schlemm's canal and a higher level of Tie2 and Prox1 compared to the values in the eye that didn't receive treatment.
Even more significantly, when the antibody was given to mice with primary open angle glaucoma, in addition to the results observed above, intraocular pressure decreased. This suggests that the antibody could be used as a medicine.
Some researchers are exploring the possibility of treating glaucoma with stem cells. These unspecialized cells can be triggered into producing specialized ones. It may one day be possible to create new cells for the eye's drainage system or new retinal ganglion cells.
Understanding Glaucoma and Improving Treatment
Human biology is complex. This is especially true at the microscopic level, where a myriad of processes occur to maintain life and keep our bodies functional. Understanding these processes can be challenging.
It's good that we have some treatments for glaucoma. Improved methods of dealing with the disease are needed, however. Fully understanding the cause or causes of glaucoma could be a huge help in the treatment of eye and nerve damage that has already occurred, the prevention of further damage, and the prevention of the disease altogether.
- Facts about glaucoma from the Mayo Clinic
- Types of glaucoma from John Hopkins Medicine
- Glaucoma information from the Canadian Association of Optometrists
- Facts about drainage in the eye from the Glaucoma Research Foundation
- Congenital glaucoma information from WebMD
- News release about lipoxins and glaucoma from the University of Berkeley, California
- A report about a potential path to glaucoma treatment via the Schlemm's canal from the Medical Xpress news service
- A doctor discusses the potential of stem cell treatment for glaucoma at the BrightFocus Foundation
Questions & Answers
© 2018 Linda Crampton