Abstract
Purpose: :
We have previously described a patient with reversible retinal dysfunction, and drug accumulation in the cornea and lens, probably caused by rifabutin, an antimycobacterial drug. In the present study we have investigated if and how rifabutin affects rabbit retina, lens and cornea.
Methods: :
Seven rabbits were treated with a daily dose (10mg/kg body weight) of rifabutin solution perorally, during a period of 12 months. Six rabbits receiving water were used as controls. Repeated full–field electroretinograms (ERG) were assessed during this period. A micro biological method was used to detect rifabutin in serum, in order to prove successful drug exposition. After terminating treatment the rabbits were sacrificed and the morphology of the cornea, the lens and the sectioned retina was studied.
Results: :
In all treated rabbits rifabutin could be detected in serum (range: 0.11–0.26 mg/L), but not in the controls. Full–field ERG demonstrated in both treated rabbits and in the controls a normal rod response. In the treated rabbits the dark adapted cone b–wave amplitude was significantly reduced (p=0.046) compared to the controls. All treated rabbits demonstrated a severe discoloring of the lens, which was not seen in the controls. Subtle corneal opacities were seen in one treated rabbit. Immunohistological studies of retinal sections stained with GAD did not demonstrate any pathological changes in morphology
Conclusions: :
Previous reports of ocular side–effects caused by rifabutin are supported by the results from this study. In treated rabbits rifabutin accumulates obviously in the lens and slightly in the cornea. Rifabutin significantly reduces cone function but does not affect either rod function or retinal morphology in rabbits.
Keywords: drug toxicity/drug effects • electroretinography: non-clinical • retina