Multimodal analysis of choroidal immune cells during ocular inflammatory disease

Summary

Uveitis, although rare, accounts for a similar amount of visual loss amongst working age people to diabetic eye disease. Treatments for uveitis have been heavily informed by animal model work which has previously investigated the retinal layer of the eye in detail. In humans, uveitis is known to occur in both the choroid and retina hence past animal work has arguably been partially disconnected from human disease. In addition, recent experiments have identified an important role for the outer covering of the brain, the dura in modulating immune responses in the brain thereby maintain immune privilege. The choroid is believed to serve a similar role in the eye.

This project aims to investigate the choroid, the outer blood vessel layer of the eye in detail. The role of the choroid in normal immune regulation, and how this is altered when uveitis occurs in the eye will be interrogated using multiple techniques. An established mice model of uveitis will be used for this. Previous choroid work has been limited due to the highly pigmented nature of the choroid. Recent innovations in imaging techniques, along with a specially selected albino mice strain, coupled with new clearing techniques that make tissues transparent can circumvent these limitations.

Murine models have been established in the Bristol Laboratory including the use here of a strain of albino mice to enhance or imaging fidelity and understanding of immune mechanisms.

Potential Impact

This project could yield new insights into the pathogenesis of uveitis which could then form the basis for new therapeutic targets in the treatment and prevention of the significant visual morbidity that can occur with this condition.

The research will also have further benefits in better understanding the origins of relative immune privilege of the eye and how dysregulation of this can lead to inflammation as seen in uveitis. This may have further external benefits in terms of understanding the conditions that generate immune privilege in other organs, as seen in the central nervous system.

Findings will be disseminated through publication and the academic literature, presentation at national or international meetings such as ARVO or FOCIS, through Above & Beyond, and PPI forums via BRC Ophthalmology.

As a current early stage research clinician with dedicated academic time on the NIHR academic clinical fellowship there is protected research time already funded to allow this project to credibly proceed and there is local experienced academic support under Prof Dick and the academic ophthalmology unit. The award will provide a valuable personal training opportunity for the applicant in both the animal model work and support the process of generating preliminary data to prepare a major grant application towards a PhD project in the same area.