Exploring novel experimental therapeutics for mitochondrial disorders of the eye

Background:

Primary mitochondrial genetic disease manifestations can involve almost all aspects of the eye. Mitochondrial disorders of the eye are often devastating genetic diseases, causing significant childhood and young adult blindness in the developed world. Mitochondrial dysfunction is also increasingly recognized as playing a causative role in the common ophthalmologic disorders in the aging retina and optic nerve. Retinal diseases are also a potential window into the wider problem of neurodegenerative disease.

Our research groups, working on this joint project, have recently synthesised novel small molecule drugs that overcome complex I inhibition to restore cellular metabolic processes and maintain retinal cell viability. Due to the chronic nature of diseases such as Leber's hereditary optic neuropathy, we seek to develop drug delivery systems for controlled release of these small molecules to sustain the rescue of cell function and prevent blindness. We will test a range a nanoparticle and soft microcarrier formulations to deliver both standard therapeutics such as Idebenone, and the previously developed novel compounds to retinal ganglion cells in culture and in ex vivo tissue culture.

Methods: By working on this project the PhD candidate will learn a range of techniques including the synthesis and characterization of drug loaded nanoparticles and cell viability analysis in vitro and ex vivo.

The aim is to make a non-toxic, nanoscale biodegradable drug delivery device that can deliver these compounds to the retina to promote rescue of retinal ganglion cells from toxic insults that model neuropathies.

The project with therefore equip the PhD candidate with a wide range of laboratory skills whilst giving them a firm knowledge base in nanoparticle drug delivery systems. Such a skill set would provide the candidate with an ideal platform for a career in academia or pharmaceutical companies.

The project will take place at Cardiff University, between the School of Pharmacy and Pharmaceutical Sciences and the School of Optometry and will be supervised by Dr Ben Newland and Prof. Marcela Votruba. 

Enquiries regarding the project: Dr Ben Newland, School of Pharmacy and Pharmaceutical Sciences, Cardiff University, and Prof Marcela Votruba, School of Optometry & Vision Sciences.

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