Rifabutin accumulates in the lens and reduces retinal function in the rabbit eye.
OBJECTIVE
To study the toxicology of rifabutin in the rabbit eye with emphasis on retinal function and histopathology.


METHODS
Seven rabbits received a daily dose of rifabutin during 15 months. Six rabbits receiving only the vehicle were used as controls. Repeated standardized full-field electroretinograms (ERG) were assessed. After discontinuing treatment, the rabbits were killed and the cornea, the lens, and the sectioned retina was studied. Immunhistochemistry directed against vimentin, glial fibrillaryacidic protein (GFAP), protein kinase C (PKC), and peanut agglutinin (PNA) was performed.


RESULTS
Rifabutin was detected in serum of the treated rabbits. During treatment, the full-field ERG demonstrated significantly reduced b-wave amplitudes in the total rod-cone response as well as in the isolated rod and cone response compared with the recordings before treatment. The control rabbits did not demonstrate a reduction of the ERG amplitudes. The treated rabbits developed a discoloration of the lens, not seen in the control group. No retinal pathology was demonstrated using immunohistochemical methods.


CONCLUSIONS
Rifabutin causes a discoloration of the lens and reduces both rod and cone function in rabbits, but does not alter retinal morphology. Previous reports on ocular side effects caused by rifabutin are supported by the results of this study.
Myers
Anna Cardiakidis
AC
Department of Ophthalmology, and daggerHospital Pharmacy, University of Lund, Lund, Sweden. anna.cardiakidis_myers@med.lu.se
Kjellström
Sten
S
Bruun
Anitha
A
Isaksson
Björn
B
Ghosh
Fredrik
F
Andréasson
Sten
S
Ponjavic
Vesna
V
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012164:Retinal Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D017828:Rifabutin / Q000493:pharmacokinetics / Q000633:toxicity*; D014746:Vimentin / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin; D017828:Rifabutin; D011493:Protein Kinase C