Mitochondrial metabolism in glaucoma
Research type
Research Study
Full title
Mitochondrial metabolism in glaucoma: Effects of the Optineurin E50K mutation and the reversal of dysfunction through pharmacological intervention
IRAS ID
359156
Contact name
Bledi Petriti
Contact email
Sponsor organisation
Moorfields Eye Hospital
Duration of Study in the UK
0 years, 11 months, 31 days
Research summary
Purpose: Glaucoma, a major cause of irreversible blindness expected to affect 80 million people globally by the end of this decade, often progresses despite normal eye pressure. Current treatments primarily focus on lowering eye pressure, which can slow disease progression but often fails to prevent vision loss. Recent research has highlighted mitochondrial dysfunction as a significant factor in both Normal Tension Glaucoma (NTG) and High Tension Glaucoma (HTG). Mitochondria, often described as the powerhouse of the cell, are crucial for energy production and overall cellular health. Our recent study, funded by Glaucoma UK, found reduced mitochondrial function in glaucoma patients and accelerated visual field deterioration in those with poorer mitochondrial function. Genetic research has identified several glaucoma-associated genes linked to mitochondrial function, including the Optineurin gene, where the E50K mutation is associated with a severe form of NTG, typically diagnosed around age 40.
Our initial findings reveal abnormal mitochondrial morphology and function in 6 family members with NTG carrying the E50K mutation. Treatment with dexpramipexole (DEX), a derivative of the Parkinson’s disease drug pramipexole, has shown promise in improving the morphology of these dysfunctional mitochondria, making them resemble normal mitochondria.Aim: To confirm mitochondrial dysfunction in E50K mutation carriers and assess whether DEX treatment can improve mitochondrial function.
Methods: We will validate our findings in a second family with the E50K mutation and recruit younger family members without NTG to determine if mitochondrial dysfunction precedes the onset of glaucoma. Additionally, we will treat fibroblasts with DEX to evaluate its effects on mitochondrial function.
Results: We anticipate confirming mitochondrial dysfunction and observing improvement in mitochondrial morphology and function with DEX treatment. If results differ, we will investigate potential reasons.
Conclusion: This study aims to validate mitochondrial dysfunction associated with the E50K mutation and explore the potential of DEX to enhance mitochondrial function, offering insights for early intervention in glaucoma
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
25/YH/0212
Date of REC Opinion
3 Nov 2025
REC opinion
Further Information Favourable Opinion