MOL PROJECTS
The Potential of Marrow Stromal Cells for the Cell-Based Therapeutic treatment of ocular diseases: 2003
Gene based treatment strategies for Diabetic Retinopathy
Generation and characterisation of an animal model for Age Related Macular Degeneration
Preclinical in vivo evaluation of sFLT secreiton gene therapy fr reitnal and choroidal neovascularisation
ANTISENSE: Charged lipophilic dendrimers: delivery of oligonucleotides with therapeutic potential
Gene therapy for the treatment of retinal dystrophy in the RPE65 knockout mouse using rAAV virus mediated gene therapy
Developmental Biology Unit (DBU) at Lion Eye Institute
Stem Cell: The Potential of Marrow Stromal Cells for the Cell-Based Therapeutic treatment of ocular
diseases
Disease: Retinal Degeneration, Dystrophy
Platform: Stem Cell
Embryonic stem cell therapy although promising, remains controversial and must still overcome the problems of rejection. Hence if an easily available source of stem cells can be found in the adult it offers a greater advantage. Several recent studies have observed that bone marrow stem cells (MCSs) can change into many different cell types including, muscle, kidney, liver, lung, brain and heart cells and it is this fact that has enabled researchers to contemplate the use of MCSs in the treatment of many disease settings as part of a cell-based therapeutic regimen. This project aims to investigate the potential of these cells to treat ocular diseases, namely retinal degenerations and dystrophies. These diseases are ideal candidates for cell-based therapy as they are characterised by the death of only one cell type in the retina namely the photoreceptors. Function can still exist in the remaining retina and the axons connecting the retina to the brain. Photoreceptor replacement via cell-based therapy may therefore aid in the restoration of some degree of vision.
Staff :
Professor P Elizabeth Rakoczy
Dr Wei-Yong Shen
Christine Hall
Sponsors:
West Australia Retinitis Pigmentosa Foundation
Lions Eye Institute
Gene Therapy: Gene based treatment strategies for Diabetic Retinopathy. 2001 - 2005
Disease: Diabetic Retinopathy, AMD,
Platform: Gene Therapy, Animal Models, in vivo and histological diagnosis, Microarray
Diabetic Retinopathy is the leading cause of blindness in people aged 20 - 74 in the developed world and is becoming a serious problem in developing countries. In Australia Diabetic Retinopathy is present in nearly one third of people with diabetes mellitus. Compared to the general population people with diabetes have a 25-fold risk of blindness. Diabetic Retinopathy is particularly common in those with Type I diabetes. Australian data show that 80% of Type I diabetics have some retinopathy by 10 years duration and almost all have retinopathy by 15 years. Additionally, one in six people diagnosed with Type II diabetes already have Diabetic Retinopathy at the time of that diagnosis. Severity of Diabetic Retinopathy worsens with duration.
This comprehensive project brings together some of the best scientific minds and their technical expertise to develop treatment strategies for Diabetic Retinopathy. The project will identify new genes that may be potentially suitable for therapies and develop appropriate animal models for the purpose of formulating and testing new therapeutic strategies.
Staff:
Lions Eye Institute
Associate Professor Chooi-May Lai
Dr Nicolette Binz
Dr Yvonne Lai
Dr Wei-Yong Shen
Dr Caroline E Graham
Joyce Eade
Jaime Mills
The University of Western Australia
Dr Lisa Tee
Pauline van Eeden
The Walter and Eliza Hall Institute of Medical Research
Dr Ken Simpson
Collaborators
Lions Eye Institute
Professor P Elizabeth Rakoczy - UWA/LEI
Professor Ian Constable
The University of Western Australia
Professor Lyn Beazley
Professor Adrian Baddeley FAA
Professor Sarah Dunlop
The Walter and Eliza Hall Institute of Medical Research
Professor Terry Speed
Curtin University of Technology
Associate Professor Erik Helmerhorst
Western Australian Institute for Medical Research
Dr Frank Koentgen
University of North Carolina
Professor Jude Samulski
University of Utah
Professor Ray Lund
Murdoch University
Associate Professor Matthew Bellgard
Sponsors:
National Health and Medical Research Council
Juvenile Diabetes Research International Foundation
Westpac Bank
Age Related Macular Degeneration: Generation and characterisation of an animal model for Age Related Macular Degeneration 2002 - 2004.
Disease: Macular Degeneration, Retinal Degeneration,
Platform: Transgenic Animal Models, Gene Expression
One of the major obstacles hindering any advance in the development of intervention strategies or therapies for these conditions is the lack of an appropriate animal model. Currently the animal models that are available for ocular disease do not fit the human AMD situation. This project aims to characterise the first animal model for Retinal Degeneration caused by abnormal functioning of the retinal pigment epithelial cells (RPE). The main role of RPE cells is the phagocytosis and digestion of the continuously growing and shed light receptor segments in the eye. Their normal functioning is vital to maintaining good vision. The availability of such as animal model will allow us to learn more about the changes that might occur in the eye leading to the development of AMD and to design strategies to prevent or delay progression of the condition.
Staff:
Lions Eye Institute
Professor P Elizabeth Rakoczy
Dr Chooi-May Lai
Dr Dana Zhang
Dr Meliha Brankov
Ms Nina Vagaja
Collaborators
University of Western Australia
Dr Vasyl Holobotovsky
Dr Douglas McKitrick
Sponsors:
National Health and Medical Research Council
Preclinical in vivo evaluation of sFLT secretion gene therapy for retinal and choroidal neovascularisation.
Disease: Neovascularisation, Diabetic Retinopathy of prematurity, Macular Degeneration, Central Retinal Vein Reocclusion
Platform: Basic Research Gene Therapy and Animal Models
The aim of this project is to develop a long-term treatment for diabetes-related retinal neovascularisation, reduce the occurrence of diabetic macular oedema and provide a highly effective treatment for age-related macular degeneration related choroidal neovascularisation before vision loss. The proposed technique would potentially be a major advance in disease management by providing a significantly improved or complementary treatment to the current therapies of laser photocoagulation, vitrectomy and photodynamic therapy. The proposed strategy utilizes recombinant virus-mediated gene delivery which basically produces the therapeutic agent specifically at the location of the disease. These studies addressing the feasibility of secretion gene therapy (SGT) will be readily applicable to our Gene Discovery Program Grant (JDRF/NHMRC 219166) that is set out to identify new anti-angiogenic genes.
Staff:
Centre for Ophthalmology and Visual Science,
University of Western Australia
Professor P Elizabeth Rakoczy
Associate Professor Chooi-May Lai
Dr Mariapia Degli-Esposti
Lions Eye Institute
Dr Meliha Brankov
Robyn Himbeck
Sponsors:
National Health Medical Research Council
ANTISENSE
Charged lipophilic dendrimers: delivery of oligonucleotides with therapeutic potential.
Disease: Choroidal Neovascularisation
Platform: Gene Therapy, Delivery Systems in vivo, Cell expression
Numerous antisense DNA sequences have been identified as potential new drugs but at this time few have progressed into the clinic due to:
i) lack of absorption / uptake; and
ii) rapid enzymatic breakdown
This project aims to address these major issues through a novel strategy involving ion pair formations of lipophilic dendrimers constructs with an oligonucleotide (OND) sequence. We will develop new dendrimers /ODN1 complexes and test them in a well-established animal model for choroidal neovascularisation (CNV).
Staff :
Lions Eye Institute
Professor P Elizabeth Rakoczy
Dr Robert Marano
Dr Meliha Brankov
Queensland University
Professor Istvan Toth
Sponsors :
National Health and Medical Research Council
Gene Therapy, Animal Models: Gene therapy for the treatment of retinal dystrophy in the RPE65 knockout mouse using rAAV virus mediated gene therapy 2001 - 2003
Disease: Retinal Dystrophy,
Platform: Adenoassociated Virus, Gene Delivery, Animal Models
RPE65 is a gene found exclusively within the retina. Presently the exact role of RPE65 is not known however recent research has shown that mutations in the RPE65 gene have been found in a number of inherited retinal dystrophies (these dystrophies include Lebers congenital amaurosis and autosomal recessive retinitis pigmentosa). It therefore appears that a functional, non-mutated RPE65 gene is essential for normal vision.
A mouse model of RPE65-related retinal dystrophies has recently been developed by producing a RPE65 "knockout" mouse breed in which the mouse's RPE65 gene has been mutated into an inactive form. Research on these mice has shown that they develop retinal dystrophies very similar to those seen in patients with mutated RPE65 genes. We propose to use these RPE65 knockout mice to test potential methods for treating the RPE65-related retinal dystrophies in patients. In particular we are studying the potential of using gene therapy to treat these diseases. The project involves delivering a new functional RPE65 gene to the retinas of the RPE65 knockout mice. The new functional RPE65 gene will then replace the inactive mutated RPE65 gene within the mouse retinas. It is predicted this will stop the mice developing retinal dystrophy. This study will improve our understanding of the RPE65-related retinal dystrophies and provide an indication of whether or not they can be treated with gene therapy.
Staff:
Lions Eye Institute
Professor P Elizabeth Rakoczy
Professor Ian Constable
Associate Professor Chooi-May Lai
Dr Meaghan Yu
Collaborators
University of Missouri-Columbia
Professor Kristina Narfstrom
NEI National Institute of Health
Dr Michael Redmond
University of Queensland
Dr Nigel Barnett
Sponsors:
National Health and Medical Research Council
Retina Australia
Foundation for Fighting Blindness
Developmental Biology Unit (DBU) at Lion Eye Institute
The DBU was established in March 2003 as a join initiative between LSSF and LEI in the form of a Research Fellowship (Brian King Research Fellowship). The DBU will establish a basic research team to study the early developmental pathways of degenerative eye diseases. One of the major causes of blindness in elderly populations in developed countries is Age Related Macular Degeneration which is characterised as abnormal growth of new and leaky blood vessels in the retina. It causes bleeding in the eye and retinal scar tissue formation which can cause diminished eyesight or blindness. Retinal pigment epithelium, the outermost layer of the retina, is understood to play a crucial role in the proper function of the underlying photoreceptors and provides a permeability barrier between retina and choroid to enable trafficking of components between these layers. Cell-cell adhesion molecules play a critical role in maintenance of proper barrier and signalling functions plus provide intracellular structural supports for epithelial cells. We believe that epithelial cells of the retina with compromised cell-cell adhesion systems will subsequently lose their function resulting in loss of vision. In a series of in vitro experiments using human pigment epithelial cells we have studied a number of key cell-cell adhesion proteins in order to understand these adhesion molecule's expression pattern and maintenance during abnormal and degenerative eye diseases. The gained knowledge from the experiments will subsequently be applied to clinically relevant cases to further elucidate their biological importance with possible development of therapeutic tools.
Staff:
Dr Reza Ghassemifar
Ms Marisa De Pinho
Collaborators:
University of Orebro
Dr Allan Sirsjo
Professor Lennart Franzen
Sponsors
Lions Eye Institute
Lions Save Sight Foundation
West Australian Retinitis Pigmentosa Foundation
