Lacrimation and corneal epithelial damage have been reported in cancer patients receiving chemotherapy with S-1: a combination of tegafur, gimeracil, and oteracil potassium. Recent studies have gradually clarified that corneal nerves contribute to homeostasis of ocular surface by facilitating protection and healing of corneal epithelium and regulating tear secretion. This study aimed to investigate the relationship between the toxic effects of S-1 on the ocular surface and alteration of corneal nerves.
S-1 (vehicle, 2 or 5 mg/kg) was administered to male Wistar rats (6 weeks old) for 28 consecutive days. As index of the ocular surface symptoms, number of blinks, tear volume, and corneal epithelial damage scores were measured. Histological analysis was performed with keratoconjunctival tissue, trigeminal ganglion, and trigeminal nucleus where corneal nerves are located.
Administration of S-1 increased the number of blinks and the corneal epithelial damage score, but unaffected the tear volume. Keratoconjunctival inflammation and corneal ulceration were absent in S-1 groups, while the density of nerve fibers in cornea, the expressions of Iba1-positive microglia in the trigeminal ganglion and trigeminal nucleus significantly increased. In conclusion, these results suggest that S-1 may induced neuromorphological changes in cornea and neuroinflammation in the corneal nerve tract with modest ocular abnormality.