Ocular tuberculosis: validation of a novel model to understand pathogenesis

Brief Lay Background

Tuberculosis (TB) is an infectious disease most often associated with the lungs, but it is also possible to get TB in the eye. This is called ocular tuberculosis, or OTB. OTB can cause sight loss if not detected early and treated appropriately.

What problem/knowledge gap does it help address

The diagnosis of OTB is challenging. To detect TB in the lungs, doctors usually test sputum or phlegm for the bacteria that cause TB. However, obtaining tissue or fluid from the eye to conduct these tests carries risks. 

To develop new diagnostic tests and treatments for OTB, a more detailed understanding of the disease-causing process in the eye is needed. The usual way that researchers obtain these insights is to study a disease in an animal model, such as rodents or zebrafish. Although existing models of OTB in these animals mirror some aspects of OTB in humans, there are differences in the structure of the eyes, and the immune response. Also, because these models are created by infecting the animals with TB, the timing and course of the disease is likely to be different to the natural course of an infection seen in humans. 

To address this, a more realistic model of OTB is required. One possible way to study natural OTB is to look at the infection in cows. Studies of naturally infected cattle have shown signs of OTB that are similar to the hallmarks seen in humans. Cows are frequently tested for TB and any animals with a positive test must be culled. Post-mortem studies of these cows could provide invaluable insights about OTB that would help scientists better understand the disease in humans. It could also provide a model for evaluating new diagnostic tests.

Aim of the research project

This project aims to assess the suitability of cattle as a model system for testing new diagnostics for OTB.

Key procedures/objectives

1. Collect post-mortem eye images and tissues from cattle to create an image database and a bank of samples for research.
2. Create image montages (compilations of images) of the eye to show the spectrum of OTB disease in cattle.
3. Use the data from these images in a sophisticated machine learning algorithm to look for common patterns or hallmarks that could be used in diagnosis.
4. Study the tissue samples from 100 cattle under a microscope to look for the presence of TB bacteria and signs of scar tissue or inflammation.  

Potential impact on people with sight loss

If successful, this project will provide extensive data and information that will tell scientists if the eye is directly infected with TB or if OTB is a result of inflammation caused by distant infection. It will also reveal hallmarks or signs of OTB that could be used to develop new diagnostic tests for OTB in humans.