Stability of the central nervous system and degenerative diseases of the retina (retinitis pigmentosa) and brain (dementia)

Lab head: Jonathan Stone
Location: Anderson Stuart N654

Our work analyses the cell biology of brain and retina, with an emphasis on the stability of the tissue, which breaks down in age-related diseases such as dementia, macular degneration and retinitis pigmentosa. Scientific work in rodent models is being expanded into clinical trials, which test neuroprotective agents - which increase stability

Lab members: Jonathan Stone Sharon Spana Sivaraman Purushothuman Charith Nandasena Sally Stowe
Funding: ARC Centre of Excellence in Vision Research, Sir Zelman Cowen Universities Fund
Research approach equipment: Our major techniques analyse the neuropathology of brain or retina, in models of dementia and retinal degeneration. This approach is complemented with functional tests, of the electroretinogram and of behaviour.

1.    Zhu, Y., K. Valter, and J. Stone, Environmental Damage to the Retina and Preconditioning: Contrasting Effects of Light and Hyperoxic Stress. Invest Ophthalmol Vis Sci, 2010. In press.
2.    Zhu, Y., R. Natoli, and J. Stone, Differential gene expression in mouse retina related to regional differences in vulnerability to hyperoxia. Molecular Vision, 2010. in press.
3.    Natoli, R., et al., Gene and ncRNA regulation underlying photoreceptor protection: microarray study of dietary anti-oxidant saffron and photobiomodulation in rat retina. Molecular Vision, 2010. In press July 2010.
4.    Falsini, B., et al., Saffron as a retinal neuroprotectant: preclinical studies and early clinical results. Proceedings of the 8th International Symposium on Ocular Pharmacology and Therapeutics, 2010.
5.    Valter, K., D.K. Kirk, and J. Stone, Optimising the structure and function of the adult P23H-3 retina by light management in the juvenile and adult. Exp Eye Res, 2009. 89(6): p. 1003-11.
6.    Stone, J. and J. Heckenlively, Animal Models of Inherited Retinal Degenerations, in The Encyclopaedia of Neuroscience, L. Squire, Editor. 2009, Academic Press: Oxford. p. 437-447.
7.    Shaw, V.E., et al., Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment. J Comp Neurol, 2009. 518(1): p. 25-40.
8.    Chrysostomou, V., K. Valter, and J. Stone, Cone-rod dependence in the rat retina: variation with the rate of rod damage. Invest Ophthalmol Vis Sci, 2009. 50(6): p. 3017-23.
9.    Chrysostomou, V., J. Stone, and K. Valter, Life history of cones in the of the rhodopsin-mutant P23H-3 rat: evidence of long term survival. Invest Ophthalmol Vis Sci, 2009. 50: p. 2407-16.
10.    Valter, K., D. Kirk, and J. Stone, The potential of ambient light restriction to restore function to the degenerating P23H-3 rat retina., in Advances in Experimental medicine and Biology, Vol.613, Recent Advances in Retinal Degeneration, E. Anderson, LaVail, MM., Hollyfield, JG., Editor. 2008, Springer. p. 193-199.
11.    Stone, J., et al., The locations of mitochondria in mammalian photoreceptors: relation to retinal vasculature. Brain Res, 2008. 1189: p. 58-69.
12.    Stone, J. and K. Valter, Roles Of Oxygen In The Stability Of Photoreceptors: Evidence From Mouse And Other Models Of Human Disease, in Eye, Retina, and Visual System of the Mouse, L. Chalupa, Editor. 2008, MIT Press. p. 559-572.
13.    Stone, J., What initiates the formation of senile plaques? The origin of Alzheimer-like dementias in capillary haemorrhages. Medical Hypotheses, 2008. 71(3): p. 347-359.
14.    Natoli, R., et al., Expression and role of the early-response gene Oxr1 in the hyperoxia-challenged mouse retina. Invest Ophthalmol Vis Sci, 2008. 49(10): p. 4561-7.
15.    Natoli, R., et al., Gene regulation induced in the C57BL/6J mouse retina by hyperoxia: a temporal microarray study. Mol Vis, 2008. 14: p. 1983-94.
16.    Eells, J., et al., Photobiomodulation for the Treatment of Retinal Injury and Retinal Degenerative Diseases, in Proceeding of Light- Assisted Tissue Regeneration and Therapy Conference, R. Waynant and D. Tata, Editors. 2008, Springer: New York. p. 39-51.
17.    Chrysostomou, V., et al., The status of cones in the rhodopsin mutant P23H-3 retina: light-regulated damage and repair in parallel with rods. Invest Ophthalmol Vis Sci, 2008. 49(3): p. 1116-25.
18.    Stone, J., Alzheimer’s Disease—The Rise and Fall of a Concept in Lies, Deep Fries and Statistics: From Radio National's Ockham's Razor, N. Williams, Editor. 2007, ABC Books: Sydney. p. 51-57.
19.    Bravo-Nuevo, A., et al., Mitochondrial DNA damage and photoreceptor death in developing and adult retina, assessed an normal and degenerative rat. Mitochondrion, 2007. 7: p. 340-6.
20.    Stone, J., T.M. Sandercoe, and J. Provis, Mechanisms of the Formation and Stability of Retinal Blood Vessels, in Ocular Angiogenesis: Diseases, Mechanisms and Therapeutics, J. Tombran-Tink and C. Barnstable, Editors. 2006, Humana Press: Totowa, NJ. p. 101-126.
21.    Jozwick, C., K. Valter, and J. Stone, Reversal of functional loss in the P23H-3 rat retina by management of ambient light. Exp Eye Res, 2006. 83(5): p. 1074-80.
22.    Geller, S., et al., Toxicity of hyperoxia to the retina: evidence from the mouse. Adv Exp Med Biol, 2006. 572: p. 425-37.
23.    Cullen, K.M., Z. Kocsi, and J. Stone, Microvascular pathology in the aging human brain: evidence that senile plaques are sites of microhaemorrhages. Neurobiol Aging, 2006. 27(12): p. 1786-96.
24.    Wellard, J., et al., Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia. Vis Neurosci, 2005. 22(4): p. 501-7.
25.    Valter, K., et al., Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section. Invest Ophthalmol Vis Sci, 2005. 46(5): p. 1748-54.
26.    Stone, J., et al., Photoreceptor stability and degeneration in mammalian retina: lessons from the edge, in Macular Degeneration: Science and Medicine in Practice, P. Penfold and J. Provis, Editors. 2005, Springer Verlag. p. 149-165.
27.    Geller, S., et al., Toxicity of hyperoxia to the retina: evidence from the mouse, in Retinal Degenerative Disease, J. Hollyfield, G. Anderson, and M. LaVail, Editors. 2005, Springer. p. 425-438.
28.    Cullen, K.M., Z. Kocsi, and J. Stone, Pericapillary haem-rich deposits: evidence for microhaemorrhages in aging human cerebral cortex. J Cereb Blood Flow Metab, 2005. 25(12): p. 1656-67.

Stability of the central nervous system and degenerative diseases of the retina (retinitis pigmentosa) and brain (dementia)

Primary supervisor: Jonathan Stone

Project of interest for Honours students include:

  1. The influence of dietary anti-oxidants on cone-rod dependence in the degenerating retina.
  2. The effectiveness of photobiomodulation in stabilising the aging retina
  3. The effectiveness of anti-oxidants and photobiomodulation in slowing neuropathology in transgenic mouse models of dementia

Discipline: Physiology