Oxygen toxicity as a factor in retinal degenerations: genetic and environmental mechanisms [ 2004 - 2006 ]

Research Grant

Researchers: Prof Jonathan Stone (Principal investigator)

Brief description This project will explore the mechanisms underlying a group of blinding diseases called Retinitis Pigmentosa (RP). They are caused by the death or degneration of the light-receptive cells of the retina of the eye (photoreceptors). It is well established that many forms of RP are caused by genetic mutations but many cases (40-50%) occur 'sporadically', i.e. without a family history. Further there is growing evidence that the rate at which genetic forms of the disease progress is strongly influenced by environmental factors, particularly light and oxygen. To analyse how these environmental factors affect the stability of the retina, we will use a range of techniques (including gene array technology) to study the molecular events which link light or oxygen stress to photoreceptor death. The work will be done in mouse 'models' of the disease. It is increasingly well established that the rodent (rat and mouse) retina and human retina share a basic structure and functional detail. These models allow intensive investigation, with results which are directly applicable to human disease. Our principal emphasis will be on three aspects of these models: (1) the molecular mechanisms induced in the retina by light stress or oxygen stress; (2) the role of mitochondria (cellular organelles essential for both cell metabolism and cell stability; and (3) genes which regulate the vulnerability of photoreceptors to oxygen stress. RP has been recognised for nearly 100 years as a leading cause of blindness in young adults. It is usually diagnosed in the young adult as a failure of night vision, but the prognosis is grim (relentlessly progressive loss of vision), and there is still no effective treatment. The work proposed will contribute to our understanding of the basic mechanisms involved, and will explore some approaches to therapy for, or at least to mitigation of the blindness of RP.

Funding Amount $AUD 269,250.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant