Oral administration of diosgenin protects optic nerve degeneration in a mouse model of normal-tension glaucoma

Abstract

Introduction

In glaucoma, degeneration of visual pathway spread whole brain area, suggesting that restoring the degenerated axons in the whole visual pathway is crucial for vision recovery. Current pharmacological therapies for glaucoma are intraocular pressure-lowering eye drops. However, the contribution of those medications to the recovery of vision loss may be small. Our previous studies revealed that diosgenin has axonal regeneration activity, and distributes in the brain after oral treatment. Therefore, we have hypothesized that the oral administration of diosgenin might better protect the visual pathway in normal-tension glaucoma because of its wide distribution in the brain.

Methods

Diosgenin was intravitreally or orally administered to optic nerve-crushed mice for 14 days. The number of retinal ganglion cells, optic nerve density, and intraocular pressure were measured. The time course of diosgenin distribution in the retina, optic nerve, and brain after oral administration was quantified using liquid chromatography-mass spectrometry.

Results

Intravitreal injection of diosgenin (0.5, 5, 50 μM, twice for14 days) provided no protective effects on the loss of retinal ganglion cells and optic nerves. In contrast, oral administration of diosgenin (1, 10, and 100 mg/kg, daily for 14 days) significantly protected against optic nerve loss but not retinal ganglion cell death. Six hours after oral administration, diosgenin reached the retina, optic nerve and brain at 6 h.

Conclusion

Oral administration of diosgenin protected the optic nerve. Diosgenin is a potential medicine that can be expected to restore the visual field in glaucoma more effectively than local intraocular administration by affecting the brain and eye.