Dr. Mansoor Sarfarazi and the Molecular Ophthalmic Genetics Laboratory is studying the genetics of glaucoma. Specifically, research is being done on adult-onset primary open-angle glaucoma caused by mutations in Optineurin and WDR36 genes.
Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN or Optineurin (for "Optic Neuropathy Inducing protein"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, non-pigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.
We have also mapped three autosomal recessive loci for Primary Congenital Glaucoma (GLC3A, GLC3B, GLC3C) and further identified the