Ischemic eye diseases are major causes of vision impairment. Thus, potential retinoprotective effects of N’N-dimethyltryptamine (DMT) were investigated. To inhibit its rapid breakdown by
monoamine-oxidase A (MAO-A) enzyme, DMT was co-administered with harmaline, a β-carboline
in the Amazonian Ayahuasca brew. Using ligation, 60 min of ischemia was provoked in eyes of rats,
followed by 7 days of reperfusion whilst animals received harmaline alone, DMT + harmaline, or vehicle treatment. After 1 week of reperfusion, electroretinographical (ERG) measurements, histological
analysis, and Western blot were performed. Harmaline alone exhibited retinoprotection in ischemia–
reperfusion (I/R) which was, surprisingly, counterbalanced by DMT in case of co-administration.
As both MAO-A inhibition and DMT increase serotoninergic tone synergistically, communicated to
be anti-ischemic, thus, involvement of other pathways was investigated. Based on our experiments,
DMT and harmaline exert opposite effects on important ocular proteins such as PARP1, NFκB, MMP9,
or HSP70, each having a critical role in a different mechanism of eye-ischemia-related pathologies,
e.g., cell death, inflammation, tissue destruction, and oxidative stress. Since DMT is proclaimed to be
a promising drug candidate, its potentially undesirable effect on eye-ischemia should be further investigated. Meanwhile, this experiment revealed the potential therapeutic effect of MAO-A inhibitor
harmaline in I/R-related eye diseases. CLICK TO REVIEW