Regeneration of optic nerve fibers with unoprostone, a prostaglandin-related antiglaucoma drug, in adult cats.

PURPOSE: We investigated the effects of unoprostone on neurite extension of cultured retinal pieces and axonal regeneration of retinal ganglion cells in the crushed optic nerve of adult cats.

METHODS: The retinal pieces were cultured with unoprostone or its primary metabolite, M1, dissolved in DMSO or polysorbate for 14 days, and the number and length of Tau-1-positive neurites and glial processes labeled with anti-glial fibrillary acidic protein antibodies were examined. After the optic nerve was crushed, unoprostone was injected into the vitreous body and the crushed site. On day 12, wheat germ agglutinin-conjugated horseradish peroxidase was injected into the vitreous body to anterogradely label the regenerated axons. On day 14, the optic nerve was excised and longitudinally sectioned. After peroxidase reaction, the number of axons regenerating beyond the crush site was examined.

RESULTS: The greatest number of neurites protruded from the cultured retinal pieces in 3 μM unoprostone and 3 μM M1. The neurite length was also the longest at 3 μM unoprostone and 3 μM M1, in which no glial processes were detected. After injections of 3 μM unoprostone, the final concentration in the vitreous humor, into the vitreous body and the crush site, the optic nerve fibers regenerated and extended beyond the crush site. In contrast, almost no fibers extended beyond the crush site after injection of phosphate-buffered saline.

CONCLUSIONS: The results indicate that intravitreal injection of unoprostone promotes regeneration of crushed optic nerve fibers in adult cats.