ABSTRACT
OBJECTIVE@#To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats.@*METHODS@#Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve.@*RESULTS@#In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment.@*CONCLUSION@#Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.
Subject(s)
Animals , Rats , Disease Models, Animal , Epothilones , Evoked Potentials, Visual , Nerve Regeneration/physiology , Optic Nerve Injuries/metabolism , Rats, Sprague-Dawley , Retinal Ganglion Cells/physiologyABSTRACT
@#Optic nerve injury is a common nervous system disease. Its basic pathological features are axonal degeneration and apoptosis of retinal ganglion cells(RGCs), which causes numbers of symptoms including visual dysfunction. Axonal degeneration, including axonal selective degradation, Wallerian degeneration induced by axonal transection, and apoptosis-induced axonal degeneration(axonal apoptosis), is an important part of neurodevelopment, axonal remodeling, and injury response process. Axonal degeneration is one of the initial steps in many traumatic neurological disorders, and damaged axons are generally unable to regenerate, which leads to neuronal cell apoptosis. Neuronal apoptosis causing the degeneration of both cell bodies and axons commonly occurs during the development of brain, as a result of various neuronal damages. Studies in recent years have confirmed that calcium is the main regulator of axonal degeneration. When an optic nerve crush(ONC)occurs, the degree of acute axonal degeneration(AAD)can be reduced by using calcium channel inhibitors to prevent the influx of calcium ions into axons, which will also improve the survival rate of RGCs and accelerate the regeneration of axons.