Abstract
Purpose: Abnormal dark adaptation is a hallmark of numerous ocular diseases. Given that the technique is noninvasive and clinically relevant, it is an attractive translatable biomarker for use in preclinical studies. In order to adapt the technique for this use, we have developed a protocol for quantifying dark adaptation in mice and applied it to measure age- and vendor-related changes in dark adaptation.
Methods: Dark adaptation was measured using electroretinography by monitoring a-wave amplitude following a dual flash photobleach. Kinetics of visual sensitivity recovery were quantified in a cohort of naive C57Bl/6 mice at 2, 4, and 6 months of age. A second cohort of C57Bl/6 mice was acquired from a different vendor and the same test was performed at 6 months.
Results: Visual recovery time was found to increase significantly from 3.6 minutes at 2 months of age to 6.3 minutes at 6 months (<0.05). In addition, we found that baseline dark adaptation ability even within a given strain varies nearly two-fold depending on the source of the mice. C57Bl/6 mice from two different vendors yielded significantly different recoveries of 6.3 and 11.2 minutes at 6 months of age (p<0.05).
Conclusions: We have quantified significant age-related dark adaptation delays in naive C57Bl/6 mice that mimic changes in the aging human population. Large differences in dark adaptation were also found to depend on the source of the mice. Mouse dark adaptation is a promising preclinical tool for developing therapies for human disease, but care must be exercised in selection of strains and ages for the studies.