Abstract
In the present study, we examined the potent retinoprotective effects of an ethanol-based extract of Aucuba japonica (AJE) and its active ingredient, aucubin, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in mice. Retinal degeneration was induced by an intraperitoneal injection of MNU (60 mg/kg). AJE (250 mg/kg) and aucubin (15 mg/kg) were orally administered for 1 week after the MNU injection. Electroretinography (ERG) and histological examinations were performed. Retinal apoptosis and oxidative DNA damage were also quantified. The retinoprotective abilities of AJE and aucubin were also assessed in primary cultured retinal cells. Morphologically, MNU induced a remarkable decrease in the outer nuclear layer, which contains photoreceptor cells. However, this layer was well preserved in the AJE- and aucubin-administered mice. The ERG responses significantly decreased in both a- and b-wave amplitudes in the MNU-injected mice. In the AJE and aucubin-treated mice, ERG responses were significantly increased. In addition, a terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) revealed that both AJE and aucubin attenuated MNU-induced photoreceptor cell apoptosis and oxidative DNA damage. Furthermore, the in vitro assay also showed that AJE and aucubin have potent anti-oxidative and anti-apoptotic activities in primary cultured retinal cells. These results indicate that AJE and aucubin have potent retinoprotective effects, and that this retinoprotective activity is as a result of the potency of the bioactive compound, aucubin. These pharmacological characteristics suggest the additional application of AJE or aucubin in the treatment of patients with retinal degenerative diseases.
Highlights
IntroductionThe dysfunction and degeneration of photoreceptors is the major reason for visual loss [1]
The dysfunction and degeneration of photoreceptors is the major reason for visual loss [1]. the detailed pathophysiology underlying this condition has not been thoroughly understood, its etiological factors include chronic inflammation and oxidative stress
60% of retinal mitochondria are located in photoreceptor cells [4], which may exacerbate photo-oxidative retinal degeneration [5]
Summary
The dysfunction and degeneration of photoreceptors is the major reason for visual loss [1]. The detailed pathophysiology underlying this condition has not been thoroughly understood, its etiological factors include chronic inflammation and oxidative stress. The excessive generation of reactive oxygen species (ROS) in the retina elicits the degeneration of photoreceptor cells and retinal pigment epithelial cells, and this is considered a causative factor of retinal degenerative diseases. Mitochondria are an important endogenous source of ROS, while exogenous ROS is generated under various conditions, such as solar radiation and smoking [2]. The retina has the highest oxygen consumption rate [3]. 60% of retinal mitochondria are located in photoreceptor cells [4], which may exacerbate photo-oxidative retinal degeneration [5].
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