The Effect of Citicoline on Ethambutol Optic Neuropathy: Histopathology and Immunohistochemistry Analysis of Retina Ganglion Cell Damage Level in Rat Model

Purpose: Ethambutol therapy in certain doses and period can cause bilateral ocular intoxication. There is no definitive therapy that has been found to prevent damage to retina neuronal cells in ethambutol optic neuropathy (EON) cases. Citicoline is thought to have a potential effect to maintain retinal neuron cells. This study aimed to analyze the effect of citicoline on damaged rat ganglion cells in EON. Methods: An experimental study of 15 Wistar rats was divided into 3 groups: the nontreatment group (A), the ethambutol (35 mg/kg/day) group (B), and the ethambutol (35 mg/kg/day) and citicoline (1 g/kg/day) group (C). Groups B and C were given treatment orally for 30 days, then a histopathology examination was performed to analyze retinal ganglion cell (RGC) density, and immunohistochemistry to assess Bcl-2 and Caspase-3 expression. Results: RGC density of rat with ethambutol intoxication that received citicoline was higher than those who did not get citicoline (P < 0.001). The rat retina ganglion layer without citicoline administration is thicker than the one with citicoline, the increase in thickness is due to the formation of vacuoles in the cytoplasm of ganglion cells. Rat with citicoline obtained higher Bcl-2 ganglion expression, and lower Caspase-3 expression compared with rat without citicoline. Conclusions: The ganglion cells damage process caused by EON can be suppressed by citicoline administration. It was proven by analyzing RGC density, ganglion layer thickness, and expression level of Bcl-2 and Caspase-3 on rat model.

citicoline; ethambutol; ethambutol intoxication; ethambutol optic neuropathy.