Neuroprotective Effect of 4-(Phenylsulfanyl)butan-2-one on Optic Nerve Crush Model in Rats

This study is to investigate the effect of coral-related compound, 4-(phenylsulfanyl)butan-2-one (4-PSB-2) on optic nerves (ON) and retinal ganglion cells (RGC) in a rat model subjected to ON crush. The ONs of adult male Wistar rat (150-180 g) were crushed by a standardized method. The control eyes received a sham operation. 4-PSB-2 (5 mg/kg in 0.2 mL phosphate-buffered saline) or phosphate-buffered saline (PBS control) was immediately administered after ON crush once by subcutaneous injection. Rats were euthanized at 2 weeks after the crush injury. RGC density was counted by retrograde labeling with FluoroGold (FG) application to the superior colliculus, and visual function was assessed by flash visual evoked potentials (FVEP). TUNEL assay, immunoblotting analysis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) in the retinas, and immunohistochemistry of ED1 in the ON were evaluated. Two weeks after the insult, the RGC densities in the central and mid-peripheral retinas in ON-crushed, 4-PSB-2-treated rats were significantly higher than that of the corresponding ON-crushed, PBS-treated rats FVEP measurements showed a significantly better preserved latency of the P1 wave in the ON-crushed, 4-PSB-2-treated rats than the ON-crushed, PBS treated rats. TUNEL assays showed fewer TUNEL positive cells in the ON-crushed, 4-PSB-2-treated rats. The number of ED1 positive cells was reduced at the lesion site of the optic nerve in the ON-crushed, 4-PSB-2-treated group. Furthermore, administration of 4-PSB-2 significantly attenuated ON crush insult-stimulated iNOS and COX2 expression in the retinas. These results demonstrated that 4-PSB-2 protects RGCs and helps preserve the visual function in the rat model of optic nerve crush. 4-PSB-2 may work by being anti-apoptotic and by attenuation of the inflammatory responses involving less ED1 positive cells infiltration in ON as well as suppression of iNOS/COX-2 signaling pathway in the retinas to rescue RGCs after ON crush injury.