Glaucoma is a common eye disease and leading cause of blindness. In glaucoma, intraocular pressure (IOP; fluid pressure within the eye) increases, damaging the optic nerve and causing vision loss. The familiar 'chronic' subtype of glaucoma develops slowly and may have few symptoms; many of those affected do not know they have the condition until it is detected during a clinical eye examination. Treatment for chronic glaucoma normally includes medication and laser surgery, and the prognosis is good.

In contrast, angle-closure glaucoma (ACG) is a severe subtype of glaucoma. Acute ACG attacks are emergencies: debilitating symptoms, including severe eye pain, headache, blurred vision, nausea and vomiting, occur suddenly. If IOP is not reduced promptly, rapid vision loss may ensue. Roughly 16 million people worldwide have ACG; 4 million people are blind in both eyes as a result.

Despite its high incidence and impact, little is known about the molecular basis of ACG. People with ACG have some common characteristics: slightly smaller than normal eyes (microphthalmia), relatively large lenses and unusually short axial lengths (distance from the front to the back of the eye). These traits increase the likelihood that the eye's drainage system, called the angle, may become blocked, leading to a build-up of fluid and high IOP. Previous work has shown that IOP elevation in ACG is not caused simply by blocked drainage, however; other physiologic mechanisms must be involved.

To learn more about the potential causes of ACG, scientists led by Simon W.M. John, a Howard Hughes Medical Institute Investigator at the Jackson Laboratory (Bar Harbor, ME) sought to identify genes associated with IOP elevation in mice. They carried out a mutagenesis screen, producing a mutation that resulted in elevated IOP in the mice. Mice carrying the mutation also had a phenotype that resembled certain features of humans with ACG (Nat. Genet. doi:10.1038/ng.813; published online 1 May 2011). The team then mapped and sequenced the mutation and found that it was located in a gene, called Prss56, that encodes a previously unidentified serine protease. Then, with collaborators Mounira Hmani-Aifa and colleagues (Université de Sfax, Tunisia), the group identified mutations in the human ortholog (PRSS56) in people with posterior microphthalmia.

The results suggest that alterations of this serine protease may be associated with a range of ocular conditions and provide a new mouse model for future research on such disorders, including ACG.