DNA Sequencing Identifies Mitochondrial Mutations in Glaucoma Patients

Diagnosis of glaucoma may be simplified by the development of a gene sequencing technique that detects mutations in the mitochondrial DNA of glaucoma patients.

Primary open-angle glaucoma occurs when optic nerve damage results in a progressive loss of the visual field. This is associated with increased pressure in the eye, which is caused by trabecular blockage. Since the microscopic passageways are blocked, the pressure builds up in the eye and causes imperceptible very gradual vision loss. Peripheral vision is affected first, but, if not treated, vision will eventually be lost entirely. Previous studies have produced evidence suggesting that glaucoma is linked to mitochondrial dysfunction.


Investigators at the University of Liverpool (United Kingdom) sought to confirm that mutations in mitochondrial DNA played a role in high-pressure primary open-angle glaucoma by analyzing new data from massively parallel sequencing of mitochondrial DNA.

To this end they recruited glaucoma patients with high-tension primary open-angle glaucoma together with ethnically matched and age-matched control subjects. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction (PCR) and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine (Life Technologies; Carlsbad, CA, USA). Life Technologies is a subsidiary of Thermo Fisher Scientific (Waltham, Massachusetts, USA).

Results revealed that in 16 of 32 patients with primary open-angle glaucoma, there were 22 mitochondrial DNA mutations consisting of seven novel mutations and eight previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes.

Senior author Dr. Colin Willoughby, professor of aging and chronic disease at the University of Liverpool, said, “Understanding the genetic basis of glaucoma can direct care by helping to determine the patient’s clinical risk of disease progression and visual loss. Increasing evidence suggests that mitochondrial dysfunction results in glaucoma and drugs that target mitochondria may emerge as future therapeutic interventions. Further studies on larger glaucoma numbers of patients are required to firmly establish the link between genetic defects in the mitochondrial genome and glaucoma development. Our research, however, has demonstrated that massively parallel sequencing is a cost-effective approach to detect a wide spectrum of mitochondrial mutations and will improve our ability to understand glaucoma, identify patients at risk of the disease or visual loss and support the development of new treatments.”

The study was published in the September 18, 2014, online edition of the journal Genetics Medicine.
Related Links:

University of Liverpool
Life Technologies
Thermo Fisher Scientific