Human Glaucoma Collaborations

To allow development of new diagnostic, therapeutic and preventative measures for glaucoma, we will exploit recently developed genomics approaches to identify new glaucoma genes. Modern genomics approaches complement genetics and will provide an unprecedented wealth of information to stimulate new glaucoma research directions worldwide. On this page: Genome-wide Sequencing Promises Rapid Advancement in Glaucoma Research, Sequencing Strategy, International Collaboration, Complementary Human and Mouse Studies, Genome-wide Sequencing Promises Rapid Advancement in Glaucoma Research. Although some glaucoma genes are identified, the majority of genetic triggers of glaucoma remain to be defined.  Current evidence suggests there are many different genes that can initiate glaucoma, so it is difficult to identify them using traditional genetic approaches. Recent technological advances, in particular massively parallel sequencing, make it possible to analyze the genetic code of all genes from an individual. Massively parallel sequencing strategies overcome some important limitations of established practices for identifying glaucoma genes. It obviates the need for specific glaucoma genes to influence the disease frequently enough for detection in genetic association studies. By globally sequencing all of the genes of individual glaucoma patients, novel variant genes that contribute to glaucoma can be identified. This will clearly be effective at  advancing understanding of disease in families.  Genome-wide sequencing projects have great potential to revolutionize understanding of glaucoma and to identify novel molecular targets for new treatments and diagnostic tests.

Sequencing Strategy

To identify glaucoma-relevant genes, we are taking advantage of the latest high throughput sequencing (HTS) technologies that enable the sequencing of the majority of the functional elements in the human genome in a timely and cost-effective manner. Currently, we are using an exome sequencing approach with whole genome sequencing and RNA sequencing in select cases.  We are currently studying families with different forma of glaucoma including congenital glaucoma, open-angle glaucoma and exfoliation glaucoma.

International Collaboration

This project is a highly collaborative effort with top genome scientists, human geneticists and ophthalmologists. We are collaborating with world experts in novel sequencing technologies and exploiting a number of the new techniques that they developed. We have established clinical and scientific collaborations throughout the world including the United States, Canada, Greece, South America, Australia, Singapore and the United Kingdom. Over the coming years, we aim to identify novel genes and biological processes to aid in the diagnosis and treatment of glaucoma.  We are happy to consider collaboration with other clinicians/scientists. The synergies within this collaboration hold greater potential for transforming glaucoma care than is possible from the efforts of each group alone.

Complementary Human and Mouse Studies

Modern sequencing and genome-wide approaches will identify many genetic variants that associate with disease.  Although some glaucoma genes will be made immediately obvious, in many, if not most, cases a variety of candidate genes will be identified. As the DNA changes that contribute to disease will often be subtle, sequencing efforts alone will not be able to definitively distinguish the causative changes from those that are present in patients but have no consequence for the disease.

Further tests will be needed to determine the specific genes that have functions that actually impact the glaucoma phenotypes. These tests constitute a process known as functional analyses. Our mouse genetics experiments will identify glaucoma genes in mice that can inform identification of the human glaucoma genes. Additionally, our expertise in genome-wide gene expression studies will help to prioritize candidate genes for further functional analyses.

Our extensive expertise in studying IOP and glaucoma in mice put us in a strong position for evaluating candidate genes.  Based on the DNA changes identified in patients, we will test the affects of specific genes on IOP and glaucoma phenotypes by studying similar changes in the equivalent mouse genes.  This will simultaneously produce valuable animal models for studying molecular mechanisms of glaucoma and testing new treatments. These mouse experiments are very important as IOP and glaucoma are very complex phenotypes and can only be fully studies in whole animals.

The mutation resources and tools that we are developing will greatly facilitate the analysis of candidate genes identified through sequencing and other genetic and genomic methods including genome wide association studies (GWAS).  We will not only test candidate genes that we identify but anticipate exciting collaborations to assess the effects of genes identified by other groups. Overall, we are well positioned to make important contributions to the discovery and characterization of new glaucoma genes and mechanisms.

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