137325-Glaucomatous neurodegeneration mechanisms in OHT patients.
Research type
Research Study
Full title
Which mechanisms confer resistance to glaucomatous neurodegeneration in ocular hypertension (OHT) patients; relevance to neuroprotection? (Pilot study)
IRAS ID
137325
Contact name
David Garway-Heath
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2014/04/21, UCL data protection registration number
Research summary
Glaucoma is a chronic progressive optic neuropathy for which the major risk factors are raised intraocular pressure (IOP) and greater age. It is the leading cause of irreversible blindness worldwide, affecting 67 million people, 10% of whom are blind in both eyes. Although raised IOP is the only known modifiable risk factor for glaucoma, patients deteriorate at widely varying rates at all levels of pressure. Emerging data from clinical and experimental studies have implicated the function of the mitochondria and oxidative stress in glaucoma development and progression. Functional changes to these systems are known to occur in ageing. Recently, original experiments from our research team on fresh lymphocytes isolated from healthy subjects and patients at the extremes of intraocular pressure (IOP) susceptibility (fast-progressing NTG subjects with mean IOP =16mmHg and non-progressing OHT patients with mean IOP =24mmHg over at least 5 years of follow-up) showed, for the first time, that OHT patients displayed increased mitochondrial efficiency when compared to age-matched NTG subjects and non-glaucomatous controls (data in preparation for publication). This entirely new and important finding indicates that mitochondrial function potentially protects these individuals from developing glaucoma.
The proposed PhD programme seeks to build on these findings and will focus on developing and characterising human dermal fibroblast lines, as a model superior to the lymphocyte model, in identifying clinically-relevant mitochondrial pathways. Fibroblasts (which are going to be obtained by skin biopsy from the study participants) maintain proliferation up to passage 20 and are not transformed cells, therefore they are an excellent material to further investigate the mechanisms that confer a) resistance to glaucoma in the OHT group and b) increased susceptibility to the disease in the NTG group.REC name
Wales REC 4
REC reference
14/WA/1080
Date of REC Opinion
28 Aug 2014
REC opinion
Further Information Favourable Opinion