Tailor made medicine: modulation of clinically significant genetic pathways for glaucoma

Dr Andrew White


Friday, 18 March, 2016 - 16:30


AOP Seminar Room 2030, Level 2, North Wing Rupert Myers Building


School of Optometry and Vision Science

Type of event: 


This seminar examines how therapy for glaucoma in genetically susceptible individuals can be targeted using a murine retinal explant model. Murine retinal explants are a model of ganglion cell specific caspase dependent apoptosis applicable to diseases such as glaucoma. Retinal explants have been used as a relatively high throughput model for investigation of pathogenesis and potential neuroprotective therapies in glaucoma. Here we describe pharmacological modulation of clinically significant genetic loci from 2 Genome Wide Association Studies in glaucoma in a murine retinal explant model. Mouse (C57BL/6) retinal explants were created and incubated at 37 degrees for between 1 and 7 days. A minimum of 3 eyes were used per experiment with the contralateral eyes used as internal control. Ganglion cell survival was quantified histologically using anti-BIII tubulin antibody in wholemount retinas. This was compared with in situ staining with anti-RNA-binding protein with multiple splicing (RBPMS) antibody. DAPI was typically used as a comparator stain. mRNA expression of pharmacological modulation of GWAS pathways significant for glaucoma was measured by rtPCR in separate experiments performed under the same conditions. We focussed in two of these genetic loci, ABCA1 and CDKN2B and were able to confer neuroprotection pharmacologically, targeting these regions. We found that ABCA1 is implicated in a caspase dependent apoptosis pathway though the exact pathway is yet to be mapped. CDKN2B is influenced by modulation of Angiotensin receptor related pathways which in turn influences caspase dependent ganglion cell apoptosis. These findings suggest that a murine ex vivo model can be a relatively rapid way to investigate modulation of clinically relevant genes for glaucoma and further investigate potential treatments in vivo. Identification of specific pharmacological modulation of apoptosis dependent pathways means that in the future we may be able to give targeted therapy to for glaucoma to genetically susceptible individuals.

Speaker: Dr. Andrew White, B.Med.Sci (Hons) MBBS PhD FRANZCO

Biography: Andrew White is a clinician scientist ophthalmologist at Westmead Hospital. His subspecialty interest is glaucoma. He was awarded First Class Honours in Medical Science in 1995 and a combined MBBS/PhD degree in 2002 from the University of Sydney. He also undertook research work at the Max Plank Institute for Biophysical Chemistry, Gottingen, Germany and the State University of New York (SUNY). Trained at the Sydney Eye Hospital, he undertook subspecialty training in glaucoma at Westmead Hospital in Sydney and Addenbrooke’s Hospital in Cambridge, UK. In 2011, Andrew was promoted to the post of Consultant Ophthalmologist at Addenbrooke’s Hospital and Senior Lecturer in Ophthalmology at the University of Cambridge. Throughout his time in the UK, Andrew undertook research at the Centre for Brain Repair, University of Cambridge. He has been invited to speak at glaucoma and ophthalmology conferences in the UK, Europe, Asia and Australasia. He has been on the organising committee for several international ophthalmology conferences. He is also actively involved in the training of medical students, registrars and fellows in cataract and glaucoma surgery. He also lectures at the UNSW School of Optometry on glaucoma and is involved in designing models of collaborative care between optometrists and ophthalmologists at both state and hopsital district level. He is a Clinical Senior Lecturer and has research affiliations with the University of Sydney at both the Save Sight Institute and Westmead Institute for Medical Research. He is a reviewer for the Journal of Glaucoma, Clinical and Experimental Ophthalmology and Translational Vision Science and Technology amongst others. Andrew is a member of the Association for Research in Vision and Ophthalmology (ARVO), Asia Pacific Glaucoma Society, Australian and New Zealand Glaucoma Interest Group (ANZGIG). He is a director of the Australian Society of Ophthalmologists, On the Associate Advisory Board for the World Glaucoma Association, on the board of the Ophthalmic Research Institute of Australia (ORIA) and is a committee member of the NSW Branch of RANZCO. He is also chair of the expert advisory panel for Glaucoma Australia.