Genetic Eye Disease Investigation Unit (GEDI)
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Team Leader -
Dr Andrea Vincent
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The Genetic Eye Disease Investigation Unit (GEDI) within the Department of Ophthalmology
was established in mid 2004 following the return of Dr Andrea Vincent from overseas
sub-speciality training in molecular ophthalmology. The overall goal is to perform
and provide quality research into genetic eye diseases, to contribute to advancement
of knowledge in the global community and to provide New Zealand individuals affected
with genetic eye diseases an opportunity for molecular diagnosis.
Both clinical and laboratory based eye genetic research is underway. Within the
existing laboratories, an Ocular Genetic laboratory has been created with the purchase
of specialist equipment for molecular genetic techniques, including two thermal
cyclers for PCR (polymerase chain reaction), a Rotorgene for High Resolution Melting
Analysis, a DNA storage facility and database, as well as Progeny software for pedigree
analysis, with utilization of UOA facilities for sequencing and GWS.
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A maculopathy with a novel mitochondrial mutation, demonstrating the clinical appearance,
and unique features on OCT and fundus autofluorescence. The functional effects of
the mitochondrial mutations are being characterised in collaboration with a Melbourne
Group.
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The pedigree of a Congenital stationary night blindness family with a novel mutation
in the NYX gene.
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Transmission Electron Microscopy (TEM) of renal biopsy in patient with an atypical
lattice corneal dystrophy and a heavy chain amyloidosis - fibrillar appearance of
the deposits (indicated by arrows) consistent with amyloid.
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Retinal arterial tortuosity (R fundus and Fluorescein angiography) in the proband
of a family with autosomal dominant anterior segment dysgenesis, retinal and intracerebral
vascular abnormalities. In collaboration with a French Group the genetic cause is
being investigated.
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Current research concentrates on 3 main areas:
1. Molecular characterisation of the Corneal Dystrophies and Keratoconus.
These corneal diseases have a strong hereditary component, and keratoconus in particular
is one of the main indications for corneal grafting, and is performed at a significantly
higher rate in the Maori and Pacific Island populations, and a number of large autosomal
dominant pedigrees have been identified within these communities, this research
should yield very satisfactory results. Patient recruitment and clinical characterization
occurs within Professor McGhee's University special clinics. Mutational analysis
of candidate corneal genes has included TGFBI, ZEB1, VSX1, in addition to linkage
analysis with genotyping to candidate loci in 2 large pedigrees with chromosomal
loci identified. In addition the features of the cornea in connective tissue disorders
such as Marfan and Stickler Syndrome is also being undertaken.
2. Inherited Retinal Dystrophy research And Establishment of a New Zealand wide
registry for inherited Retinal Disease.
This resource will incorporate phenotypic and genotypic data, permitting identification
of patients should gene or phenotype specific clinical trials become available,
and also acts as a superb research resource. The current Ocular Genetics Fellow,
Dr Leo Sheck, is undertaking his MD in particular looking at the phenotypic differences
observed with imaging modalities in a number of genetically characterised retinal
maculopathies, as well as research into the mitochondrial basis of retinal and optic
nerve disorders.
3. Molecular Characterisation of A New Zealand Glaucoma Population.
Patient recruitment is ongoing, including willing participants from Prof Danesh-Meyer's
glaucoma clinics. A baseline mutational database is established, with MYOC, OPTN,
CYP1B1 and WRD36 analysed . This has identified unique NZ pedigrees who may allow
identification of further glaucoma genes. In addition local, Australasian (Melbourne,
Perth )and International collaborations ( Belgium, Northern Ireland, Switzerland,
France, Harvard) exist with research underway into Blepharophimosis syndrome, Inherited
Eye Movement disorders, Juvenile Pagets Disease, Mitochondrial dysfunction, and
connective tissue abnormalities.
Staff
Currently one research technician, Ms Amanda Richards is employed, and to date,
two Ocular Genetic Clinical Research Fellows, and 9 summer students have undertaken
projects within the Department, with collaboration with other Clinical Ophthalmology
fellows, medical students and Ophthalmology trainees. Further technical and scientific
expertise is utilised within the department.
The presence, and future of the Ocular Genetic Research Facility within this progressive
environment of the Department of Ophthalmology relies on the existing collaborative
interaction between clinicians and scientists within the Department, and can only
be enhanced by provision of opportunities for multi-disciplinary approaches to resolving
the burden of eye disease and vision impairment.
To date financial support has been obtained through the University of Auckland Research
Committee, Save Sight Society, Maurice and Phyllis Paykel Trust, School of Medicine
Foundation, Glaucoma New Zealand, the Vice Chancellor's Development Fund, Alcon
New Zealand, Auckland Medical Research Foundation, The Ombler trust, and Retina
New Zealand.
