Ocular Tuberculosis: A One Health Multiparameter Approach to Diagnosis

In humans, tuberculosis (TB) can occur in the eye as the sole site of disease activity. Ocular TB (OTB) causes intraocular inflammation which is sight threatening and classically presents with one of three recognised clinical phenotypes. In order to understand the immune and inflammatory processes that occur, and to develop appropriate treatment regimens for OTB in humans an animal model would be of use. Of particular relevance is the bovine model. Cattle infected with Mycobacterium bovis (the causative agent of bovine TB) present with highly homologous immunopathology to humans with TB. In preliminary studies of eyes taken from M. bovis-infected cattle it was found that ocular signs of TB were present in a proportion of animals.
Bovine eyes taken post-mortem from cattle that have been diagnosed with TB will be examined in this project. This will be carried out using a purpose built retinal camera and images will be analysed (in collaboration with Epipole Ltd) to identify whether cattle develop a similar ocular phenotype to humans with OTB. We will characterise TB lesions in collaboration with veterinary opthalmic graders and with colleagues at Google Deep Mind/Moorfields Eye Hospital to establish a machine learning algorithm (autoML) to assist in selecting eyes with potential disease. Imaging of disease-control eyes and normal, uninfected cattle will assist in establishing the limits of ’normal’ in the bovine fundus.
Once eyes with disease are identified, studies of the immune cell composition of the eye and examination of inflammatory molecule expression using established immunohistochemical techniques (in collaboration with APHA) will be carried out. Molecular analysis of the uvea to establish presence and quantity of mycobacterial DNA will also be performed.
The data generated from the bovine study will be analysed and compared with available data from ongoing human clinical cases in collaboration with Moorfields Eye Hospital. There is a clear translational link to humans with ophthalmic TB and the outcome of the project may influence how clinical cases are managed, diagnosed and treated. With potential benefits to both veterinary and human medicine the project fits well within a One Health remit.

Other projects available:
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 10th January 2020 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships