Speaker
Description
Inflammation of eye known as Uveitis is responsible for 15% of blindness in the western world, particularly affecting the working age population. Uveitis can be induced by infection but often is associated with autoimmunity that is not well understood. Inflammation occurring in the posterior region of the eye may cause blindness as it disrupts the delicate structure of the retina and damages photoreceptors. Biopsies and direct characterisation of the immune cell populations in the retina are rare and difficult to obtain.
Formalin-fixed paraffin embedded (FFPE) archived enucleated and eviscerated human uveitis eyes collected via routine clinical care over the last 30 years at Moorfields Eye Hospital were used for this study. FFPE-chorioretinal biopsies with a histopathological diagnosis of uveitis, were sourced capturing the active inflammatory stage of uveitis. These tissues underwent multiplexed immunohistochemistry using IBEX adapted for FFPE imaging and incorporating autofluorescence quenching. IBEX is an open-source method that incorporates iterative fluorescent immunohistochemical staining. Over 25 various immune cell and structural markers have been imaged on 10 uveitis samples. Tissues were segmented using DeepCell Mesmer and processed using SPACE R package for spatial analysis revealing immune cell populations and their spatial configurations.
Infectious and presumed autoimmune uveitis cases exhibited unique immune cell populations and exhibit spatially distinct features. Equally, active stage uveitis captured in chorioretinal biopsies versus late-stage chronic diseases in eviscerated or enucleated samples also had consistent differences in the immune cell localisation to the retinal and choroidal structures.
Multiplexed immunohistochemistry on these archived ocular samples provides a new understanding of the clinical pathology of uveitis. The immune cell profile and distribution of each of the subtypes can be compared to clinical data, while the spatial configuration of such as tertiary lymphoid structures and granulomas may indicate areas of therapeutic investigation for the development of targeted treatments for uveitis.
Lay Abstract
Uveitis is a serious inflammation inside the eye and is responsible for about 15% of blindness in Western countries, often affecting adults of working age. When this inflammation occurs at the back of the eye, it can cause severe damage to the retina and lead to permanent sight loss. Because biopsies from the eye are difficult to obtain, relatively little is known about the exact immune cells involved in different types of uveitis.
This study uses a rare collection of archived eye tissues gathered over the past 30 years at Moorfields Eye Hospital. These include whole eyes removed due to severe disease and even small biopsies taken during active inflammation. The tissues were analysed using an advanced imaging method called IBEX, which can show more than 25 different immune and structural markers on the same sample. Computer based tools were then used to identify immune cells and map where they sit within the retina and surrounding tissues.
The results show clear differences between infectious and autoimmune uveitis, and between early active disease and late stage chronic damage. Understanding which immune cells are present, and where, may help identify new treatment targets and improve personalised care for people with uveitis.
| Lay Title | Mapping immune cells in archived human eyes with Uveitis |
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| Role | PhD Student |