Identifying cellular and physiological factors associated with sub-clinical ocular inflammation and discomfort

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The key research goals in this project are:

• To investigate the diurnal dynamics and characteristics of the ocular surface immune system in healthy eyes.
• To characterise the structural, physiological and immunological interplay between immune cells and sensory nerves at the ocular surface.

The details

Have you ever noticed a change in comfort of your eyes as the day progresses? Some people suffer from red and painful eyes when their eyes are strained, or when they are wearing their contact lenses. This ocular surface discomfort typically increases towards the end of the day.

Recent data from research undertaken by the supervisory teams at the Universities of Melbourne and Manchester support changes to the eye during contact lens wear and dry eye disease, in the form of ocular surface inflammation and ocular discomfort. Both aspects are thought to derive from the same source: an increased sub-clinical ocular inflammatory response induced by the presence of a contact lens or altered tear function.

The discomfort experienced during contact lens wear and dry eye disease appears to be time-dependent (i.e. worse towards the end of the day). Interestingly, ocular surface immune cell populations and certain tear inflammatory proteins also follow a homeostatic diurnal pattern. This project hypothesises that normal immune cell diurnal patterns at the ocular surface are perturbed by contact lens wear and dry eye disease, which may have a pathogenic role in the discomfort response experienced by some individuals.

To consider this hypothesis, this project will investigate the diurnal (i.e. morning versus evening) features of ocular surface immune cells, beginning with a characterisation of this phenomenon in healthy adults. These studies will involve in vivo confocal microscopy (a state-of-the-art, non-invasive, high-resolution imaging technique that enables direct visualisation of the sensory nerves and immune cells in the living human eye) and immunological tear film analyses. This research will characterise the relationship between tear mediators and immune cell changes in the cornea, conjunctiva and meibomian glands (being the major ocular surface components) to establish homeostatic diurnal rhythms. This work involves participant recruitment, clinical examinations and digital image analysis at the Melbourne and Manchester locations.

In addition to the clinical studies, a range of pre-clinical investigations will be undertaken to allow for cell phenotyping analyses. Mouse models of ocular surface inflammation will be used to correlate morphological changes in immune cell populations with expression of phenotypic markers. These findings will provide clinically translatable information that will shed light on the functional relevance of morphological changes to immune cells in the human ocular surface, such as those evident during contact lens wear and dry eye disease.

The graduate researcher on this project is: Ching Yi Wu

Supervision team

• The University of Melbourne: Associate Professor Laura Downie, Dr Holly Chinnery
• The University of Manchester: Dr Carole Maldonado-Codina, Professor Philip Morgan