About Primary Congenital Glaucoma
Primary congenital glaucoma (PCG) is a devastating early childhood eye disease accounting for 5% of childhood blindness and 18% of blind school registry. The eye maintains its shape via pressure from internal fluid (aqueous humor) that is produced by the ciliary body and circulates throughout the chambers of the eye.
In patients with glaucoma, the drain for this fluid (made up of the trabecular meshwork and Schlemm’s canal) does not function correctly. This allows the fluid to build up in the eye, increasing the pressure, which will damage the sensitive structures involved in light-sensing in the eye, such as the retina and optic nerve. If left untreated, blindness will invariably occur.
Primary congenital glaucoma (PCG) is a devastating early childhood eye disease accounting for 5% of childhood blindness and 18% of blind school registry. The eye maintains its shape via pressure from internal fluid that circulates throughout the chambers of the eye. In patients with glaucoma, the drain for this fluid does not function correctly. This allows the fluid to build up in the eye, increasing the pressure which will damage sensitive structures involved in light-sensing in the eye, such as the retina or optic nerve. If untreated, blindness invariably occurs.
PARTICIPATE IN A PRIMARY CONGENITAL GLAUCOMA RESEARCH STUDY
Our research on primary congenital glaucoma (PCG) has also utilized the latest next-generation sequencing technology (exome/whole-genome sequencing) to identify genes harboring small changes/variants that may be causal for the development of PCG. The discovery of new genes associating with a disease increases our understanding of the biology behind the condition, allows for molecular diagnostic testing and genetic counselling, and uncovers molecular pathways which might be targeted by potential therapies in the future.
This publication outlines the work performed by members of the Young lab that led to the identification of mutations in the TEKgene as the second largest contributor to PCG. The lab was able to demonstrate that the TEK variants found in 10 families with PCG resulted in the loss of TEK protein function, impacting a signaling pathway critical for the correct formation of the drainage structures of the eye.
This publication was the culmination of research performed by a large number of labs collaborating to analyze possible areas of the genome that may be associated with various abnormalities associated with glaucoma. Specifically, the study implicated several genes as potentially influential for intraocular pressure levels and optic nerve structures. This study has provided insights into possible molecular mechanisms underlying glaucoma.
Optic disc changes are one of the hallmarks of glaucoma pathogenesis. This study, in collaboration with the International Glaucoma Genetics Consortium, studied the genomes of more than 20,000 individuals in order to search for genes that may be influencing these optic disc changes. The results contribute to an expanding body of knowledge of the molecular pathways involved in the development of glaucoma.
Intraocular pressure elevation is one of the first steps in the pathogenesis of glaucoma, eventually resulting in optic nerve damage and vision loss. This work centered on the analysis of more than 35,000 people to find regions of the genome that were inherited along with an increase in intraocular pressure. In addition, genome sites that were inherited along with glaucoma were also investigated and many sites were found to be the same as for increased intraocular pressure. This work helped to illuminate the interplay between intraocular pressure and glaucoma on a deeper, genetic level. This work was also performed in collaboration with the International Glaucoma Genetics Consortium.