The effects of ageing on ocular surface integrity
AffiliationOptometry and Vision Sciences
Document TypeMasters Research thesis
Access StatusThis item is embargoed and will be available on 2021-10-17.
© 2019 Manikkuwadura Eranda Harshan De Silva
Purpose: Ageing is recognised as a major risk factor for several ocular pathologies, including dry eye disease. The aim of this thesis was to characterise the specific effect of ageing on key ocular surface parameters, in humans and mice. We hypothesised that there would be common ageing effects in both species that paralleled the pathophysiological features observed in dry eye disease. Method: The animal study involved healthy C57BL/6 female mice, aged 2 months (young, n=10) and 22 months (aged, n=10). Clinical assessments included measurements of corneal sensitivity (Cochet-Bonnet aesthesiometry, which is a contact corneal aesthesiometer), tear secretion (Phenol red thread test), tear film osmolarity (TearLab osmometer) and corneal thickness (optical coherence tomography). The anatomical integrity of the corneal nerves was examined ex vivo (using immunohistochemistry) by quantifying nerve density in the superficial epithelium (superficial terminals) and sub-basal plexus. The density and tree area of resident epithelial dendritic cells (DCs) were assessed using immunofluorescence and confocal microscopy. For the clinical study, 37 healthy male and female participants (15 male participants and 22 female participants) were recruited, and divided into four age categories: 20-35 years, 36-50 years, 51-65 years, and >65 years. Participants underwent a comprehensive characterisation of ocular surface health, including quantification of tear osmolarity, blink rate, slit lamp biomicroscopy and corneal sensitivity (using non-contact corneal aesthesiometry). In vivo confocal microscopy (IVCM) was performed to quantify a range of corneal nerve parameters, microneuroma density and DC density, in the central and peripheral cornea. Results: In the animal study, aged mice had significantly higher tear secretion, lower corneal sensitivity and a thicker corneal stroma but thinner epithelium compared with young mice. There was no significant inter-group difference for tear osmolarity. Aged mice showed a significantly lower cornea nerve density, in both the superficial terminals and sub-basal plexus, relative to young mice. DC density and morphology were similar in both age groups. In the human study, older age was associated with a reduction in central corneal sensitivity to a room temperature air stimulus, but not to a cold temperature stimulus. Tear osmolarity remained within normative ranges (<308mOsmol/L) in all age groups, although it was relatively higher in this parameter amongst individuals aged 36 to 50 years, compared to the 20 to 35 year olds (p = 0.0047). A range of ocular surface parameters, including corneal sub-basal nerve plexus density, DC density and microneuroma density were not subject to ageing effects but showed eccentricity-dependent differences. Blink rate and most standard clinical biomicroscopic findings were not significantly different between age groups. Conclusion: Ageing has differential effects on ocular surface parameters. A reduction in corneal sensitivity, and a relative maintenance of corneal DC density, was evident in older eyes in both species. The apparently disparate findings in relation to corneal nerve density between mice and humans may relate to the established limitations of in vivo imaging techniques, particularly with respect to image resolution. These findings, relating to ocular surface changes with physiological ageing, are of value for understanding the potential contribution of the ageing process to ocular surface diseases.
Keywordscornea; ageing; ocular surface
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