Mutations in the gene for myocilin (MYOC), a secreted protein with unknown functions, are associated with juvenile and adult-onset primary open angle glaucoma – the leading cause of irreversible blindness. Cell culture and mouse studies suggest that MYOC mutations prevent myocilin secretion into the aqueous humor, and that its accumulation inside cells results in a stress response.
Rachel Kuchtey, M.D., Ph.D., assistant professor of Ophthalmology and Visual Sciences, and colleagues tested this hypothesis in patients. They sequenced the MYOC gene and assessed myocilin protein levels in aqueous humor samples obtained from glaucoma and control patients at the time of glaucoma or cataract surgery. They report in the June European Journal of Medical Genetics that myocilin protein was detected in all control aqueous humor samples, but was nearly undetectable in samples from a patient with a newly identified de novo MYOC mutation.
The findings in patients are consistent with studies showing that MYOC mutations reduce myocilin secretion, and suggest that patients with these mutations may benefit from treatments that relieve the cellular stress response.
This research was supported by grants from the National Institutes of Health (EY020894, EY007065) and from Research to Prevent Blindness.
