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Long-term intraocular toxic effects of topical mitomycin C in rabbits
Purpose:
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.
Insights
Toxic intraocular effects of mitomycin C (MMC) applied externally to rabbit eyes were found to be long-lasting. Histological examination at 6 and 12 months revealed persistent damage, suggesting significant ocular toxicity.
Area of Science:
- Ophthalmology
- Toxicology
- Cell Biology
Background:
- Mitomycin C (MMC) is a chemotherapeutic agent with potential applications in ophthalmic surgery.
- Understanding the long-term intraocular toxicity of externally applied MMC is crucial for patient safety.
Purpose of the Study:
- To evaluate the reversibility of toxic intraocular effects following extraocular application of mitomycin C (MMC).
Main Methods:
- Sponges soaked with varying concentrations of MMC (0.1 and 0.2 mg/ml) were applied to the sclera of rabbit eyes.
- Control eyes received sponges soaked with balanced salt solution.
- Histological examination was performed at 6 and 12 months post-application.
Main Results:
- MMC-treated eyes showed persistent pathological changes in the ciliary epithelium, including cellular irregularities and mitochondrial swelling.
- Damage to ciliary body nerves and thickening of capillary basement membranes were observed.
- The observed pathological changes were consistent between the 6- and 12-month examination points.
Conclusions:
- Toxic intraocular effects of extraocular MMC application in rabbits are dose-dependent and do not appear to be reversible over time.
- These findings highlight the significant toxic potential of MMC, although direct human impact requires further investigation.