1. Glaucoma Research Boosting optic nerve energy to slow glaucoma Ian Trounce Principal Investigator CERA Wagstaff Fellow RVEEH

2. The burden of glaucoma 67 million world-wide 6 million estimated blind 7 million out-patient visits in the USA 150,000 people in Australia $145 million in direct health costs to Australia Significant number of Australians with glaucoma are undiagnosed.

3. Eye pressure lowering is the only treatment proven to be effective in glaucoma Lowering eye pressure does not always prevent progression Cannot restore optic nerve tissue once lost Problems with current treatments

4. Professor Jonathan Crowston, Principal Investigator Translational research – Molecular and cellular research – Experimental models Rodents, rabbits – Clinical research Glaucoma Research Unit

5. ‘Burns’ fuels (food) Produces energy (ATP) Produces byproduct ‘free radicals’ Wears out with age The cell’s powerhouse: The mitochondrion

6. Mitochondria: Power generators of our cells IN: Fuel Carbohydrates Fats Proteins O 2 OUT: Energy (ATP) Free radicals CO 2 H 2 0 Heat

7. Mitochondrial DNA - Maternal inheritance

9. Douglas C. Wallace – University of Pennsylvania

10. Complex I defect in glaucoma -Link to Parkinson’s disease? -Is it mitochondrial DNA-linked? -New collaboration with Doug Wallace, Univ. Pennsylvania

11. The optic nerve - Glaucoma Dopamine neurons - Parkinson’s disease Highly energetic nerve cells with long axons are prone to age-related decline

12. Exercise (and fasting) allow old optic nerves to recover from a pressure injury

14. 2.25 cd.s/m 2 3.0 cd.s/m 2 P=0016P=0.0014 PhNR change at 1 month IOVS 2013

15. Mitochondrial energy generation is impaired in some glaucoma patients Diet moderation and exercise improve optic nerve resilience Is this due to increased mitochondrial ‘health’? Genetic analysis of mitochondrial DNA in glaucoma subjects underway Can we identify subjects with genetic markers who may respond to ‘mitochondrial boosting’ therapies? Summary

16. Can we drive increased Mitochondrial turnover to “recharge the batteries” Dietary restriction Exercise Resveratrol Other drugs e.g. Fibrates Metformin Rapamycin

17. Thank you Funding Wagstaff Bequest (RVEEH) DHB Foundation Brockhoff Foundation (ANZ Trustees) – Leber Optic Atrophy stem cell study Mason Foundation (ANZ Trustees) – The ‘good’ Alzheimer protein & the ageing eye Michael J. Fox Foundation for Parkinson’s disease – A mitochondrial PD model National Health and Medical Research Council