Genes causing pediatric glaucoma contribute to future stroke

Every year in Canada about 50,000 people suffer from a stroke, caused either by the interruption of blood flow or uncontrolled bleeding in the brain. While many environmental risk factors exist, including high blood pressure and smoking, stroke risk is also frequently inherited. Unfortunately, remarkably little is known regarding stroke’s genetic basis.

A study from the University of Alberta, published in the Journal of Clinical Investigation, extends knowledge of stroke’s genetic underpinnings and demonstrates that in some cases it originates in infancy.

The research identifies two genes (FOXC1 and PITX2) that cause cerebral small vessel disease, a “pre-stroke” condition that increases the risk of future stroke up to ten times. It was found the mutations result in cerebral small vessel disease in patients as young as one year of age. By inhibiting these genes in lab models, the researchers induced comparable brain vascular changes and gained key insights into the mechanisms involved.

The two genes are known to cause a type of pediatric glaucoma by affecting the normal migration of vital stem cells to the eye. These same stem cells also play a pivotal role in the formation of brain blood vessels, forming the smooth muscle in artery walls that is essential for structural integrity. A reduction in the number of these cells impairs vascular stability, and leads to cerebral small vessel disease. This in turn substantially increases the long term risk of stroke.

By demonstrating for the first time that a proportion of stroke has a developmental basis, the research has identified a very wide timeframe (five decades or more) between the onset of cerebral small vessel disease and a stroke occurring. This discovery provides ample opportunity for therapeutic intervention - currently with improved blood pressure control, statins, etc. - and the expectation that the findings will stimulate research to develop treatments targeting potential solutions.

What is childhood glaucoma?

Glaucoma is a condition in which the normal fluid pressure inside the eyes (intraocular pressure, or IOP) slowly rises as a result of the fluid aqueous humor - which normally flows in and out of the eye - not being able to drain properly. Instead, the fluid collects and causes pressure damage to the optic nerve (a bundle of more than 1 million nerve fibers that connects the retina with the brain) and loss of vision. Glaucoma is classified according to the age of onset. Glaucoma that begins before the child is 3 years old is called infantile or congenital (present at birth) glaucoma. Glaucoma that occurs in a child is called childhood glaucoma.
What causes childhood glaucoma?

Glaucoma occurs when the fluid drainage from the eye is blocked by abnormal development or injury to the drainage tissues, thus, resulting in an increase in the intraocular pressure, damage to the optic nerve, and loss of vision.

There are many causes of childhood glaucoma. It can be hereditary or it can be associated with other eye disorders. If glaucoma cannot be attributed to any other cause, it is classified as primary. If glaucoma is a result of another eye disorder, eye injury, or other disease, it is classified as secondary.

Equally, the findings may provide novel insights in eye disease where the research originated. Some patients with pediatric glaucoma caused by the genes FOXC1 and PITX2 suffer gradual visual deterioration despite excellent surgical control of intraocular pressure. It has always been assumed that ongoing damage to the eye was responsible. However, the identification of extensive brain vascular changes provides an alternative explanation, and is expected to influence clinical management for these patients.


Genes causing pediatric glaucoma contribute to future stroke The research involved 11 collaborating Canadian, American and European laboratories, with funding provided by the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation, Natural Sciences and Engineering Research Council (NSERC) and the National Institutes of Health (NIH). It was led by Ordan Lehmann, professor in the departments of ophthalmology and medical genetics at the University of Alberta].

To arrange an interview with Ordan Lehmann, please contact:


Ross Neitz, communications associate
Faculty of Medicine & Dentistry
780-492-5986 (office) .(JavaScript must be enabled to view this email address)

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