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Methods of modulation of mitochondrial function in glaucoma


   Department of Eye and Vision Science

  Ms Neeru Vallabh, , Dr Amy Chadwick,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Background:

Glaucoma is a common, irreversible, optic neuropathy affecting the vision of predominantly older adults that slowly progresses over a period of years. Glaucoma affects over 2% of those over 40 years, rising to 4% of white and 15% of black populations by the age of 80. In the UK glaucoma affects over half a million individuals, with over quarter a million over 65. It is a leading cause of visual morbidity, accounting for 12% of blind registrations, a likely significant underestimate of true glaucoma related blindness1. Increasing research has demonstrated the role of mitochondrial dysfunction in the aetiology of glaucoma2. Given the central role of mitochondria, as both a source and target of oxidative stress, therapeutic approaches that target mitochondria may provide a means of protecting the eye from this condition. A recent clinical trial where patients received nicotinamide supplements found improvements in inner retinal function and a trend for improved visual field was observed with 27% improving on nicotinamide and fewer deteriorating compared to placebo3.

Furthermore, the fast and reliable diagnosis of glaucoma is an ongoing uncertainty for clinicians, particularly as the rate of progression of the condition varies between patients. This results in difficulty determining appropriate allocation of finite health resources  Metabolomics has the potential to identify biomarkers, including mitochondrial metabolites, that can be used for glaucoma diagnosis and prognosis. These results would allow for earlier diagnoses, when more visual function can be spared4

Aim:

·        To evaluate the role of supplements in improving mitochondrial function in glaucoma

·        To evaluate the role of metabolomics as a non invasive biomarker for glaucoma evaluation

Methods:

Tissue samples and clinical data will be acquired from cadaveric donor tissue and patients undergoing ocular surgery at Liverpool University NHS Foundation Trust. The successful student will acquire skills in cell culture, flow cytometry and qPCR. In addition, cellular bioenergetic changes such as mitochondrial capacity, rates of glycolysis and oxidative phosphorylation, will be assessed using Seahorse XF analyser. Evaluation and optimisation of metabolites will be performed at the Centre for Metabolomic Research. The students will join a team of interdisciplinary researchers and acquire research training in study design, metabolomics, cell culture and translational research. Students will also have the opportunity to attend clinical sessions and observe glaucoma surgery.

Research Environment:

The Department of Eye and Vision Science (DEVS) was established in 2010 as a development from the Ophthalmology Research Unit set up in 1993. It is part of the Institute of Life Course and Medical Sciences, one of four research Institutes focusing on delivering research excellence as part of the strategic direction of the University. The Department is formed around a partnership with St. Paul’s Eye Unit (SPEU), Liverpool University Hospitals Foundation NHS Trust (LUHFT) to study the mechanisms, prevention, early detection and treatment of eye diseases. The Centre for Metabolomic Research (CMR) is part of the Department of Biochemistry and Systems Biology and is based on the Liverpool campus in the Institute of Systems, Molecular and Integrative Biology (ISMIB). The successful applicant will have the opportunity to join a vibrant and expanding multidisciplinary team of scientists studying diseases of the eye and a clinical unit with an international reputation for excellence and innovation.

For any enquiries relating to the opportunity or enquiries regarding applying, please contact Neeru Vallabh on:


Funding Notes

We are looking for self-funded students or students who have secured funding from an independent body. There is no financial support available from Liverpool for this study. Please see website for PhD student fees at the University of Liverpool: View Website
The successful applicant will be expected to have funding in place for the tuition fees (check University of Liverpool website), consumables/bench fee (£ 15000 per annum) and living expenses during their stay in Liverpool.

References

1. King AJ, Reddy A, Thompson JR, Rosenthal AR. The rates of blindness and of partial sight registration in glaucoma patients. Eye (Lond). 2000;14 ( Pt 4):613-619. doi:10.1038/eye.2000.152
2. Kamel K, Farrell M, O’Brien C. Mitochondrial dysfunction in ocular disease: Focus on glaucoma. Mitochondrion. 2017;35(May):44-53. doi:10.1016/j.mito.2017.05.004
3. Hui F, Tang J, Williams PA, et al. Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial. Clin Experiment Ophthalmol. 2020;48(7):903-914. doi:10.1111/ceo.13818
4. Barbosa-Breda J, Himmelreich U, Ghesquière B, Rocha-Sousa A, Stalmans I. Clinical Metabolomics and Glaucoma. Ophthalmic Res. 2017;59(1):1-6. doi:10.1159/000479158

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