Long-term intraocular toxic effects of topical mitomycin C in rabbits.
OBJECTIVE
To detect whether toxic intraocular effects of mitomycin C (MMC) after extraocular application are long-standing or are reversible over time.


METHODS
We placed sponges soaked with MMC on the intact sclera of rabbit eyes after incision of the conjunctiva. Controls received sponges soaked with balanced salt solution. Concentrations of MMC were 0.1 and 0.2 mg/ml. The eyes were examined histologically after 6 and 12 months.


RESULTS
In all MMC-treated eyes, pathologic changes of the ciliary epithelium were present, which included irregular cell surfaces, intracytoplasmatic vacuoles, swelling of mitochondria, and disorganization of the endoplasmic reticulum. Nerves within the ciliary body also exhibited mild-to-moderate loss of axons in nonmyelinated nerves and increase of interstitial collagen deposition. Capillaries within the ciliary body consistently had a thickened basement membrane, which was arranged in two to three layers in multiple areas. The changes seen were similar in eyes examined at 6 and 12 months after application of MMC.


CONCLUSIONS
These results suggest that toxic intraocular changes are dose dependent and do not recover over time. The impact of these findings on humans is unclear, but may further emphasize the high toxic potential of MMC.
Department of Ophthalmology, University of Cologne, Germany.
H
H
Mietz
K
K
Addicks
W
W
Bloch
G K
GK
Krieglstein
D000287:Administration, Topical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002924:Ciliary Body / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008137:Longitudinal Studies; D016685:Mitomycin / Q000633:toxicity*; D009186:Myelin Sheath; D009412:Nerve Fibers / Q000187:drug effects / Q000648:ultrastructure; D009802:Oculomotor Nerve / Q000187:drug effects* / Q000473:pathology; D009883:Ophthalmic Solutions; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D012590:Sclera / Q000187:drug effects* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D009883:Ophthalmic Solutions; D016685:Mitomycin