Glaucoma ResearchBoosting optic nerve energy to slow glaucoma

Ian TrouncePrincipal Investigator CERAWagstaff Fellow RVEEH

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.

• 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

• Professor Jonathan Crowston, Principal Investigator• Translational research

– Molecular and cellular research– Experimental models

• Rodents, rabbits– Clinical research

Glaucoma Research Unit

• ‘Burns’ fuels (food)• Produces energy (ATP)• Produces byproduct

‘free radicals’• Wears out with age

The cell’s powerhouse: The mitochondrion

Mitochondria: Power generators of our cells

IN:

Fuel•Carbohydrates•Fats•Proteins•O2

OUT:

Energy (ATP)Free radicalsCO2

H20Heat

Mitochondrial DNA- Maternal inheritance

Douglas C. Wallace – University of Pennsylvania

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

The optic nerve- Glaucoma

Dopamine neurons- Parkinson’s disease

Highly energetic nerve cells with long axonsare prone to age-related decline

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

2.25 cd.s/m2 3.0 cd.s/m2

P=0016 P=0.0014

PhNR change at 1 month

IOVS 2013

Mitochondrial energy generation is impaired in some glaucoma patients

Diet moderation and exercise improve optic nerve resilienceIs this due to increased mitochondrial ‘health’?

Genetic analysis of mitochondrial DNA in glaucoma subjects underwayCan we identify subjects with genetic markers who may respondto ‘mitochondrial boosting’ therapies?

Summary

Can we drive increased Mitochondrial turnover to “recharge the batteries”

Dietary restriction

Exercise

Resveratrol

Other drugse.g.FibratesMetforminRapamycin

Thank you

FundingWagstaff Bequest (RVEEH)DHB Foundation Brockhoff Foundation (ANZ Trustees) – Leber Optic Atrophy stem cell studyMason Foundation (ANZ Trustees) – The ‘good’ Alzheimer protein & the ageing eyeMichael J. Fox Foundation for Parkinson’s disease – A mitochondrial PD modelNational Health and Medical Research Council