BUT and CTT tests are useful methods in screening high susceptible NOD mice. Cutting lines at BUT < or = 2 seconds and CTT < or = 4 mm/min provide a good balance between the assurance of susceptibility and the maximization of use of NOD mice for the study of Sjögren's syndrome.
Fingolimod is a promising prodrug in attenuating multiple sclerosis and prolonging survival of organ allograft, with many other protective effects. Its mechanism of action is related to the internalization of sphingosine 1-phosphate receptors (S1PRs). Our previous study indicated that fingolimod eyedrops was efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of non-obese diabetic (NOD) mice. In the current study, we evaluated potential adverse effects of fingolimod eyedrops. Inbred 10-week-old BALB/c mice were randomly divided into four groups, fingolimod-treated groups at three different concentrations (0.01%, 0.1% and 0.5%) and a negative control group without intervention. Our results showed that in the 0.5% fingolimod group, adverse effects such as photophobia, catacleisis and corneal oedema were observed after 1 week of treatment. 1 month later, corneal opacity, oedema and neovascularization persisted till the mice were killed 2 months later. In contrast, there was no significant abnormality in the negative control group, and 0.01% and 0.1% fingolimod-treated groups. During a 2-month treatment period, we did not detect fingolimod, nor significant change in blood cells in peripheral blood, nor pathological changes in retina and systemic organs. Combined with our previous study and the current results, we recommend that an optimal range of safe and effective concentration of fingolimod as eyedrops is between 0.005% and 0.1%.
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