The Genetics of Glaucoma | Glaucoma Research Foundation

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Glaucoma is the term used for a group of diseases that irreversibly damage the optic nerve, leading to vision loss and ultimately, if untreated, blindness. Genetic factors are considered to play a key role in all major forms of glaucoma.

In recent years the curtain that has blocked our view of the genetic cause of glaucoma has begun to lift, ushering in a new era in our understanding of the fundamental causes of glaucoma.

Primary open-angle glaucoma (POAG) is the most common type of glaucoma and has no obvious abnormality in the eye that points to a cause. Although mutations in several genes, including myocilin, optineurin, and CYP1B1, have been reported to cause POAG, these genes account for less than 10% of cases worldwide. In the past 2 years, large scale genetic studies that have examined the blood samples of thousands of glaucoma patients have been instrumental in the discovery of more common genetic risk factors for POAG. A risk factor is something that doesn’t always lead to a condition but increases the risk of having that condition. For glaucoma, these genetic factors include changes in the DNA sequences (near or in the genes such as caveolin 1 and 2 (CAV1/CAV2), CDKN2B antisense RNA, TMCO1, SIX1/SIX6, and LRP12/ZFPM2 genes) or actual loss of DNA (TBK1 and GALC), and several different genes have been implicated. How these genes cause or influence the likelihood of developing POAG is of major interest.

Glaucoma is often thought of as a disease of middle age or older adults. However there are many inherited forms of glaucoma that affect young children. Primary congenital glaucoma (PCG) is the most common childhood glaucoma affecting children from birth to age 3 and is a major cause of blindness in this young population. Mutations in the CYP1B1 gene have been found to cause PCG in children worldwide and are the dominant genetic cause for glaucoma in children in the Middle East and central Europe. In the United States only 15% of children with PCG have a mutation in CYP1B1, so there are ongoing efforts to identify additional causes in these young patients. Other types of glaucoma related to maldevelopment of the eye occur in older children – the genes implicated in these forms of glaucoma play a key role in the development of the eye, so when they malfunction they cause abnormalities in the eye’s fluid drainage system which leads to elevated eye pressures and glaucoma. The genes currently known to be associated with these forms of glaucoma include PITX2, PITX3, FOXC1, FOXE3, PAX6, LMX1B, and MAF.

Primary angle-closure glaucoma (PACG) is the second most common form of glaucoma and affects over 16 million people globally. In this form of glaucoma the drainage angle closes over time, blocking the pathway to the drainage system and causing high eye pressures. Very recently a large scale genetics study identified genetic variants that are associated with this form of glaucoma. These variants are in or near PLEKHA7, PCMTD1/ST18, and COL11A1. How these genes contribute to this form of glaucoma is not clear.

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