Photoreceptor and vision protective effects of astragaloside IV in mice model with light-evoked retinal damage

Cone cell-enriched macular degeneration is a major cause of functional vision deterioration. Astragaloside IV (Asg IV), an active triterpenoid saponin component with properties of anti-oxidative and anti-apoptotic damage, which benefit retinal tissue and capillaries. But, the nutraceutical therapeutic effects on functional vision have not been fully evaluated. In this study, mice were administrated to high-intensity light exposure after either receiving a vehicle or Asg IV (0.05, 0.5, and 50 mg/kg, BID). During this time, their spatial-visual performance, visual acuity (VA), and visual contrast sensitivity function (VCSF) were measured using the behavioral optomotor reflex method. Morphological changes in the retina were determined by histological examination. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in both VA and VCSF, whereas the retina tissue exhibited loss of cone cell density and severe cone-specific opsin misplacement. In contrast, prophylactic oral Asg IV (0.5, and 50 mg/kg, BID)-treated exerted protective and improvement effects against light-evoked deterioration of functional vision. Asg IV treatment significantly improved the thresholds of VA and VCSF. In particular, Asg IV (50 mg/kg, BID) modulated and increased the survival of the photoreceptors, especially the cone cells, which targeted and enhanced the high spatial frequency-characterized VCSF. In contrast, the cellular protective effect of Asg IV (50 mg/kg, BID) on photoreceptors was significantly reversed by synchronous injection of a glucocorticoid receptor (GR) antagonist (mifepristone). This study demonstrated the major neuroretina-protective effect and functional vision-improving effect of Asg IV in vivo.