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

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Glaucoma research

Glaucoma Research

Boosting optic nerve energy to slow glaucoma

Ian Trounce

Principal 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.


Problems with current treatments

  • 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


Glaucoma Research Unit

  • Professor Jonathan Crowston, Principal Investigator

  • Translational research

    • Molecular and cellular research

    • Experimental models

      • Rodents, rabbits

    • Clinical research


The cell’s powerhouse: The mitochondrion

  • ‘Burns’ fuels (food)

  • Produces energy (ATP)

  • Produces byproduct‘free radicals’

  • Wears out with age


Mitochondria: Power generators of our cells

  • IN:

  • Fuel

  • Carbohydrates

  • Fats

  • Proteins

  • O2

OUT:

Energy (ATP)

Free radicals

CO2

H20

Heat


Mitochondrial DNA

- Maternal inheritance



  • Complex I defect in glaucoma

  • Link to Parkinson’s disease?

  • Is it mitochondrial DNA-linked?

  • New collaboration with

  • Doug Wallace, Univ. Pennsylvania


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

The optic nerve

- Glaucoma

Dopamine neurons

- Parkinson’s disease



Phnr change at 1 month
PhNR change at 1 month

P=0016

P=0.0014

3.0 cd.s/m2

2.25 cd.s/m2

IOVS 2013


Summary

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?


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

Dietary restriction

Exercise

Resveratrol

Other drugs

e.g.

Fibrates

Metformin

Rapamycin


Thank you
Thank you the batteries”

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


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