Corneal opacities in mice exposed to repeated contact procedures during ocular examinations

Abstract

Background

Cystine/glutamate exchanger (xCT) knockout mice are reported to exhibit an oxidative shift in the plasma cystine/cysteine ratio reminiscent of that seen in human plasma of ageing individuals. This suggests that the xCT knockout mouse is a model of accelerated ageing. The aim of this study was to examine the progression of age‐related pathologies in the ocular tissues of wild‐type mice and compare this to the xCT knockout mice.

Methods

Wild‐type and xCT knockout mice were examined longitudinally or as separate groups of animals at six weeks, three months, six months, nine months, and 12-months of age. All groups of mice were anaesthetised, intraocular pressure measured using the iCare TONOLAB rebound tonometer and eyes examined using the Micron IV system.

Results

While the aim of the study was to determine if xCT knockout mice developed age‐related pathologies earlier than wild‐type mice, it was inadvertently discovered in the longitudinal cohort of animals, that the eyes developed corneal lesions in both groups of animals by six months of age, which obscured examination of the lens and retina. These lesions were not characteristic of age‐related pathologies, but rather due to an external stressor. Lesions in the xCT knockout mice developed at an earlier age compared to wild‐type mice, suggesting that loss of xCT exacerbates damage to the cornea, most likely caused by the rebound tonometer. When the same ocular procedures were performed on separate cohorts of mice of specific ages, no corneal lesions were detected for both groups of mice.

Conclusions

While it may seem advantageous to examine the same cohort of mice to monitor the development of age‐related pathologies, the type of ophthalmic tests conducted needs to be carefully considered to avoid introducing pathologies that are inadvertently a result of the examination process itself.

Key words:

• ageing
• cornea
• cystine/glutamate exchanger knockout mice
• repeated contact procedures

ACKNOWLEDGEMENTS

We would like to thank the following agencies for supporting this work: The HOPE Foundation for Research on Aging, The Faculty Research Development Fund, The University of Auckland, The Maurice and Phyllis Paykel Trust, the New Zealand Optometric Vision Research Foundation and the Auckland Medical Research Foundation.

Additional information

Funding

The HOPE Foundation for Research on Aging

The Faculty Research Development Fund

Auckland Medical Research Foundation

Maurice and Phyllis Paykel Trust

New Zealand Optometric Vision Research Foundation

University of Auckland