EYE GENETICS

Group leaders

Group Members

Robyn Jamieson MBBS FRACP PhD (Syd) CG (HGSA), Unit Head
John Grigg MBBS MD (Syd) FRANZCO FRACS
Frank Billson MBBS FRANZCO FRACS
Rebecca Storen BSc, Research Assistant
Ivan Prokudin BSc, PhD, Research Officer
Wan Yi Ng MBBS (Hons), Postgraduate Student
Rebecca Greenlees BSc (Hons), Postgraduate Student
Saira Mahomed Yousoof BSc, MMedSc, Postgraduate Student

Research Activity

Genetic eye disorders contribute to blindness and partial-sightedness for many with visual disability in our community. Our research studies in genetic eye disease focus on ocular conditions including cataracts (clouding of the lens), glaucoma (raised pressure in the eye and optic nerve abnormality), retinal anomalies (disorders affecting the back of the eye) and microphthalmia or anophthalmia (small or absent eye). All of these conditions can lead to visual disability or blindness and in all there are few or limited treatment options. This research work aims to discover disease genes important in these conditions, and the functions of the proteins they encode. By understanding the detailed protein functions, we will then be able to develop better treatments to vastly improve the management of these conditions.

In this research programme we are studying patients and families who have eye conditions, using high resolution genomic techniques to identify the underlying disease genes. We also study the mouse as a model to understand the detail of the functions of disease genes which cause abnormalities of eye development. We have collaborative links with the Children’s Medical Research Institute (CMRI), the Western Sydney Genetics Programme and the Discipline of Paediatrics and Child Health at the Children’s Hospital at Westmead (CHW).

Projects

The genetic basis of microphthalmia and anophthalmia
Jamieson, Grigg, Storen, Greenlees

Microphthalmia (small eye) and anophthalmia (absent eye) cause significant visual disability and the associated features including cataract and glaucoma also contribute to this vision impairment. The underlying genetic causes are unknown in the majority of cases. In a family with two children affected with anophthalmia, we discovered a novel mutation in the SOX2 gene. One of the normal parents was found to be mosaic for the gene change. Hence, SOX2 mosaicism in a parent can lead to anophthalmia recurrence in a family. Our investigation of two mouse models with microphthalmia, indicates a role for the regulation of Wnt signaling in eye development, particularly in retinal and iris development.

High-resolution genomic studies in cataract, glaucoma, anterior segment dysgenesis and retinal dystrophies
Mohamed Yousoof , Prokudin, Ng, Greenlees , Storen, Grigg, Jamieson

The human genome project has led to rapid advances in analysis of the human genome. We are using highresolution genomic techniques to identify novel disease genes in patients with eye disorders including cataract, glaucoma, anterior segment and retinal abnormalities. Several novel candidate disease genes have been identified and are undergoing characterization. Cell-based assays and production of animal models are being undertaken for investigation of strong candidates.

Genetics of macular dystrophy
Jamieson, Grigg, Prokudin, Ng

The macula is in the centre at the back of the eye, and is essential for detailed and colour vision. Many elderly patients suffer from macular degeneration. In some familial cases, genes important in maintenance of macular health have been identified. We have
ascertained several families with macular disease, where the genetic cause is not known. We are undertaking detailed characterization of the macular features and genetic investigations to identify candidate disease genes.