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National Glaucoma Research
Current Award

Dr. Alex Hewitt

Alex Hewitt, M.B.B.S. (Hons), M. Med. Sci., Ph.D.

Centre for Eye Research Australia, The University of Melbourne
Melbourne, Australia

Title: Refinement of an Induced Pluripotent Stem Cell Model for Retinal Ganglion Cell Apoptosis
Non-Technical Title: Development of a Patient-Specific Model of Glaucoma

Co-PI(s):
Alice Pébay, Ph.D.
Centre for Eye Research Australia
Mirella Dottori, Ph.D.
University of Melbourne

Acknowledgements: This grant is made possible by a bequest from the Esther Katcher Irrevocable Trust.
Duration: July 1, 2013 - June 30, 2015
Award Type: Standard
Award Amount: $99,488

Summary:

In the past two years, Drs. Hewitt, Pébay, and Dottori have made important genetic discoveries, which have dramatically improved the understanding of how glaucoma develops. Their research has led to the rapid identification of people who are at least three times more likely to develop glaucoma. The team is now working to further understand how these genes cause disease in individual patients. This “personalized medicine” technique has become possible due to recent breakthroughs in stem cell technology, enabling the production of stem cells from easily-accessible adult tissue. This means they can change those stem cells into cells which cannot be easily obtained from a living person, such as the retina, to examine the development and progression of a disease. They are using this technique to uncover the functional pathways in glaucoma, by comparing retinal ganglion cells that were derived from adult cells from patients with differing genetic risk profiles.

Details:

Recent breakthroughs in stem cell technology have led to the ability to generate stem cells from adult tissue. This offers the unique ability to study the disease-causing processes in tissue, such as the retina, which cannot be easily obtained from living patients. Drs. Hewitt, Pébay, and Dottori are investigating the disease-associated mechanisms of glaucoma, by comparing the molecular profile of retinal ganglion cells generated from glaucoma patients with differing genetic risk profiles.

The team of Drs. Hewitt’s, Pébay’s, and Dottori has recently identified two new genes associated with the risk of developing glaucoma (called TMCO1 and CDKN2BAS). The team is now specifically investigating the role(s) of the high risk CDKN2BAS and TMCO1 gene variants on promoting retinal ganglion cell death. This is being undertaken by generating “induced pluripotent stem cells” from glaucoma patients who have high or low risk genetic variants, as well as from age-matched people who do not have any known glaucoma risk factors. These stem cells will then be changed into retinal ganglion cells for investigation of disease-specific changes. Each cell derived from glaucoma patients and normal controls will be analyzed for their specific response to injury. The application of this technology in humans is novel and could lead to new therapies.

Investigator Biography:

Dr. Alex Hewitt is a clinician-scientist and leads the Clinical Genetics Unit at the Centre for Eye Research Australia, University of Melbourne. During medical training he completed a BMedSci (Hons) degree investigating the outcomes of cataract surgery for people living in remote areas of the Northern Territory. He obtained his Ph.D. investigating the molecular and phenotypic associations for open-angle glaucoma from Flinders University of South Australia in 2009. Alex completed formal Ophthalmology training at the Royal Victorian Eye and Ear Hospital in 2011, and then spent one year as the Novartis Genetics Fellow at the Lions Eye Institute in Western Australia. He returned to Melbourne in 2013 to take up the position of Unit Head.