Opioid transport into the central nervous system is crucial for the analgesic efficacy of opioid drugs. Thus, the pharmacokinetics of opioid analgesics such as morphine have been extensively studied in systemic circulation and the brain. While opioid metabolites are routinely detected in the vitreous fluid of the eye during postmortem toxicological analyses, the pharmacokinetics of morphine within the retina of the eye remains largely unexplored. In this study, we measured morphine in mouse retina following systemic exposure. We showed that morphine deposits and persists in the retina long after levels have dropped in the serum. Moreover, we found that morphine concentrations (ng/mg tissue) in the retina exceeded brain morphine concentrations at all time points tested. Perhaps most intriguingly, these data indicate that following chronic systemic exposure, morphine accumulates in the retina, but not in the brain or serum. These results suggest that morphine can accumulate in the retina following chronic use, which could contribute to the deleterious effects of chronic opioid use on both image-forming and non-image-forming visual functions.
Keywords: blood-brain barrier; blood-retina barrier; hypothalamus; mass spectrometry; morphine; opioids; pharmacokinetics; retina.