Keratopathy in rats after treatment with tilorone.
According to clinical reports, the antitumor drug tilorone induces corneal opacities in patients. The present communication shows that keratopathy can be experimentally reproduced in rats and describes the cellular alterations underlying the corneal opacities. Tilorone was applied either orally (60-90 mg/kg) for several weeks or topically (2%) for a few days. Biomicroscopic examination performed after treatment for 6 weeks or longer revealed fine punctate opacities throughout the corneal stroma. Ultrastructurally, the keratocytes were swollen due to large, optically empty vacuoles in the cytoplasm. Similar, albeit smaller, vacuoles were also numerous in the endothelium and less frequent in the epithelium. Histochemical experiments showed that the cellular alterations represented lysosomal storage of polyanionic substances, most probably sulfated glycosaminoglycans, thus mimicking the cytological picture of mucopolysaccharidosis. Upon discontinuation of drug treatment, the alterations tended not to recede. This keratopathy in rats is part of a generalized mucopolysaccharidosis-like disorder induced by tilorone.
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Lüllmann-Rauch
D000818:Animals; D003318:Corneal Opacity / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005449:Fluorenes / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013994:Tilorone / Q000009:adverse effects* / Q000627:therapeutic use
D005449:Fluorenes; D013994:Tilorone