Research outline - Retinal & Cerebral Neurobiology Laboratory

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Overview of research program

Our work concerns degenerative diseases of the central nervous system, in particular the retinal dystrophies (retinitis pigmentosa, age-related macular degeneration), age-related dementia (Alzheimer’s disease) and Parkinson’s disease. We manipulate the cell biology of retina or brain to minimize stress to neurons, and reduce and even reverse the progression of the disease.
Selected animal (rodent) models enable the syatematic exploration of each approach. Collaborations with clinicians are beginning the translation of our work to the treatment of human disease.

The work is organized in 2 major streams, one concerning the retina and one concerning the brain. Because the retina is more accessible to treatment, most of our approaches to regulating the cell biology of central nervous system neurones have been trialled in the retina – oxygen levels, photobiomodulation, antioxidants and (for the retina) light. In rodent models we have succeeded in slow degenerations reliably, but also – relying on the ability of damaged photoreceptors to self-repair – we have demonstrated recovery of visual function. In a model of Parkinson’s disease we have shown that photobiomodulation penetrates cranial tissues with sufficient power to protect deep brain structures.

Technically, our work extends from the analysis of gene expression to clinical trials.

Major funding sources

  • ARC Centre of Excellence in Vision Research
  • Sir Zelman Cowen Universities Fund

Selected publications

Falsini B, Piccardi M, Minnella A, Savastono C, Fiorani L, Maccarone R, Romeo S, Silva R, Stone J, Bisti S (2010) Saffron as a retinal neuroprotectant: preclinical studies and early clinical results. Proceedings of the 8th International Symposium on Ocular Pharmacology and Therapeutics . In press

Valter K, Kirk D, Stone J (2009) Optimising the adult P23H-3 retina by light management in the juvenile and adult. Exp Eye Res In press

Shaw V, Spana S, Ashkan K, Benabid A, Stone J, Baker G, Mitrofanis J (2009) Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared (NIr) light treatment. J Comp Neurol In press

Chrysostomou V, Valter K, Stone J (2009) Cone-rod dependence in the rat retina: variation with the rate of rod damage. Invest Ophthalmol Vis Sci 50: 3017-3023

Chrysostomou V, Stone J, Valter K (2009) Life history of cones in the of the rhodopsin-mutant P23H-3 rat: evidence of long term survival. Invest Ophthalmol Vis Sci 50: 2407-2416

Stone J (2008) What initiates the formation of senile plaques? The origin of Alzheimer-like dementias in capillary haemorrhages. Medical Hypotheses 71: 347-359

Natoli R, Provis J, Valter K, Stone J (2008) Gene regulation induced in the C57BL/6J mouse retina by hyperoxia: a temporal microarray study. Mol Vis 14: 1983-1994

Eells J, DeSmet K, Kirk D, Wong-Riley M, Whelan H, Ver Hoeve J, Nork T, Stone J, Valter K (2008) Photobiomodulation for the Treatment of Retinal Injury and Retinal Degenerative Diseases. In: Waynant R, Tata D (eds) Proceeding of Light- Assisted Tissue Regeneration and Therapy Conference, vol I. Springer, New York, pp 39-51

Chrysostomou V, Stone J, Stowe S, Barnett NL, Valter K (2008) The status of cones in the rhodopsin mutant P23H-3 retina: light-regulated damage and repair in parallel with rods. Invest Ophthalmol Vis Sci 49: 1116-1125

Cullen KM, Kocsi Z, Stone J (2006) Microvascular pathology in the aging human brain: evidence that senile plaques are sites of microhaemorrhages. Neurobiol Aging 27: 1786-1796

Major collaborations

Professor Silvia Bisti, University of L’Aquila (Italy): Dietary antioxidants as a retinal neuroprotectants

Professor Janis Eells, University of Wisconsin Milwaukee: Photobiomodulation as a retinal neuroprotectants

Dr. Benedetto Falsini, Policlinico Gemelli, Catholic University of the Sacred Heart, Rome: Clinical trials of dietary antioxidants in age-related macular degeneration

Professor Eli Keshet, Hebrew University of Jerusalem: Transgenic mouse models of cerebrovascular dementia

Professor Peter McCluskey and Dr. John Grigg, Save Sight Institute, University of Sydney: Clinical trials of light restriction and antioxidants in retinal dystrophies.

Professor John Mitrofanis, Discipline of Anatomy and Histology, University of Sydney: Photobiomodulation as a neuroprotectant in Parkinson’s disease.