Research

NEWSFLASH!

AUSTRALIAN INHERITED RETINAL DISEASE REGISTER AND DATA BANK

With the support of its State bodies, Retina Australia is providing funds to expand the Inherited Retinal Disease Register and DNA Bank held in Western Australia at the Sir Charles Gairdner Hospital, to include all persons within Australia with an inherited retinal eye disease, and selected blood relatives who wish to participate.

The procedure is simple - a sample of blood or saliva is taken, and forwarded to the IRDR laboratory where the DNA is extracted and held in secure conditions.

This material will form a databank of samples which will be made available to any gene therapy researcher in the world who seeks to make use of it. In the future, when funds are available, the DNA material will be ‘sequenced’ to ascertain the individual’s specific errant retinal gene, or in the case of blood relatives, whether or not they carry the gene.

For people living in NSW, information about participation in the Inherited Retinal Disease Register can be obtained by contacting Retina Australia (NSW).

Intensive research has been fostered by the world’s RP groups and is making headway in unravelling the mysteries of RP and will hopefully soon lead to effective treatment and ultimately a cure.

Current approaches to research include -

Understanding the structure and function of the retinal cells and their interaction with connections to the brain.
Modification of the diseased retinal cells by genetic manipulation.
Replacement of the diseased retinal cells with stem cells - derived either from embryos or adults.
Insertion of electronic equipment to function as a bionic eye.

Significant valuable research in Australia is contributing to the global effort in trying to overcome RP and other degenerative eye diseases. Australian research is funded by Retina Australia, through its grants program, and the National Health and Medical Research Council (NH&MRC).

The Board of Retina Australia has made grants totalling $139,700 to four research projects being undertaken at Australian universities during 2011. This amount has been possible due to the extremely hard work done by state RP organizations in raising funds for research, and to the generous supporters who continually respond to their fundraising efforts.

A further grant was awarded to Dr Erica Fletcher, University of Melbourne

whose continuing research is encouraging. She explains:

“Our currently funded NHMRC grant is aimed at examining in detail how the molecule, ATP, causes photoreceptor death, and whether blockade of this class of molecule slows photoreceptor death in two animal models of retinal degeneration. We propose that in those with RP or animal models, death of rods causes the release of large amounts of ATP which subsequently causes death of neighbouring rods and cones.

“What we have achieved so far: We have made considerable progress in understanding the mechanism and time course by which ATP kills photoreceptors. In addition we have found that compounds that block the action of ATP slow photoreceptors down in animal models of retinal degeneration, and that photoreceptor loss is reduced in an animal that lacks expression of receptors for ATP.

“What we plan to do in 2011:

For 2011, we will be expanding this work, and in particular will be concentrating on the mechanism by which ATP affects photoreceptors in a novel transgenic mouse (P2X7null/rd1 mouse).”

Dr Fletcher and Dr Una Greferath, who was also supported last year, spoke at the Annual General Meetings of RA (NSW) and RA (Victoria) at the end of the year. They have kindly written a report of their work for RODS readers and for the RP organizations throughout Australia.

Retina Australia also allocated grants to:

The Eye Genetics Research Group at The Children’s Hospital at Westmead and the University of Sydney.

Chief Investigators: Associate Professor Robyn Jamieson; Dr John Grigg.

Centre for Eye Research Australia (Affiliated with the University of Melbourne and the Royal Victorian Eye and Ear Hospital).

Chief Investigators: Professor Robyn Guymer; Dr Lyndell Lim.

The University of Western Australia.

Chief Investigators: Professors David M Hunt and Shaun P Collin.

RECENT DEVELOPMENTS IN RETINAL DEGENERATION

Associate Professor Erica Fletcher, Dr Ursula Greferath, University of Melbourne

There have been considerable advances in our knowledge of the pathogenesis of inherited retinal degenerations over the last five years that have lead to the development of some very promising treatments. Below, we have summarized some of our own findings examining new animal models of inherited retinal degeneration, ways to slow photoreceptor death and also novel ways of replacing lost photoreceptors.

1) New animal models: Most research into the mechanisms of photoreceptor death have utilized animal models that carry mutations in rod associated proteins (e.g., rhodopsin). Whilst this work has been very important, it has little relevance to some of the rarer forms of retinal degeneration such as Leber Congenital Amaurosis. Recently, we have identified a novel mouse that replicates many of the features of one form of Leber Congenital Amaurosis. This mouse called the Histidine decarboxylase null mouse develops severe changes in the outer retina because the support cells of the retina lack proteins that maintain the correct position of the rods and cones. These mice will be used by us now to study some of the rarer forms of retinal degeneration.

2) Slowing photoreceptor death: much of our work over the last few years has been directed at examining whether dying rods release a toxic factor that affects neighbouring photoreceptors. Our work has shown that the energy molecule, ATP is released in large amounts from dying rods and accelerates the death of neighbouring cells. We have tested two drugs known to block the action of ATP, and shown them to slow photoreceptor death in a mouse model of retinal degeneration. In addition, we have found that the rate of photoreceptor death is slowed in transgenic mice that lack the expression of the receptor to ATP. Agents that block the action of ATP are under development by large pharmaceutical companies because of their potential role in controlling some forms of pain. We hope our work expands the possible uses of these compounds into the ophthalmic area.

3) Novel ways of replacing lost photoreceptors: The two most exciting developments to restore vision in those who have few photoreceptors remaining are the development of electronic implants, and the use of gene therapy to target visual pigments to the remaining neurons of the inner retina. There are currently two large groups in Australia developing electronic implants to restore vision. One group is designing retinal implants: a wide-field device that sits underneath the retina, and another high visual acuity device that is designed to target the output neurons of the retina. It is hoped that trials for the wide view device in patients will begin in the next year. The high visual acuity device is currently undergoing preclinical testing. A second group, based at Monash University is designing an implant to be inserted into the visual area of the brain. This device is intended to restore vision in those who have no remaining ganglion cells or an intact optic nerve. Currently this device is undergoing extensive preclinical development.

Gene therapy has been used to target visual pigment to inner retinal neurons. The inner retina of those with inherited retinal degeneration is usually intact. By using gene therapy, inner retinal neurons can become light sensitive, performing the duties of photoreceptors. These studies are very exciting because the technology can be used in most patients with inherited retinal degeneration irrespective of the specific genetic cause of the disease.

In summary, over the last few years our knowledge of inherited retinal degeneration has increased dramatically, to the point where treatments are now being tested in patients, with exciting results.