Abstract
Retinal ischemia-reperfusion (RIR) injury causes neuronal degeneration and initiates various optic nerve diseases. This study aimed to investigate the synergistic neuroprotective effect of rasagiline and idebenone against RIR injury. A combination of rasagiline and idebenone was administered intraperitoneally immediately after establishment of the RIR model. Treatment with the combination of the two drugs resulted in a significant restoration of retinal thickness and retinal ganglion cells. Apoptosis of cells in ganglion cell layers was also ameliorated, suggesting that the effect of the two drugs was synergistic and the expression of brain-derived neurotrophic factor increased. Furthermore, idebenone and rasagiline induced the expression of Lin28A and Lin28B, respectively, which resulted in a reduced expression of microRNAs in the let-7 family and an increased protein output of Dicer. The data obtained from gene overexpression and knockdown experiments indicated that let-7 and Dicer were necessary for the synergistic neuroprotective effect of the two drugs. Our findings suggested that combination therapy with rasagiline and idebenone produced a synergistic effect that ameliorated RIR injury and restored visual function. In addition, the combined treatment provided neuroprotection via enhancement of the selective regulation of let-7 by Lin28A/B. These findings implied that a treatment with the combination of rasagiline and idebenone is a feasible treatment option for optic nerve diseases.
Highlights
Retinal ischemia is a consequence of reduced retinal blood circulation, which affects the normal functions of the eye tissues and occurs because of an insufficient supply of nutrients and oxygen to the retina
Rasagiline and idebenone synergistically protected visual function against Retinal ischemia-reperfusion (RIR) injury Optomotor response and light-dark exploration tests were performed to evaluate the visual function of the RIRinjured mice when rasagiline was jointly administered with alpha-lipoic acid (ALA), lutein or idebenone
No significant differences in visual acuity or the percent of time spent in the light chamber were observed between the group treated with rasagiline and ALA and the group treated with rasagiline or ALA (Figure 1A and 1B)
Summary
Retinal ischemia is a consequence of reduced retinal blood circulation, which affects the normal functions of the eye tissues and occurs because of an insufficient supply of nutrients and oxygen to the retina. This results in neuronal damage, morphological degeneration of the retina, and impaired retinal function [1]. Immediate reperfusion rapidly restores the blood supply; it causes further damage to the retina by stimulating inflammation and an excessive generation of reactive oxygen species (ROS) This accelerates neuronal cell death [2]. Together with neuronal death and reduced retinal function [9, 10], RIR injury often results in visual impairment and leads to vision loss owing to a lack of effective treatments
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