This in vitro study evaluated whether Astragalus polysaccharide (APS) protects 661W photoreceptor cells from hypoxic injury (2% O₂ vs. 21% O₂), testing APS concentrations of 100–2000 μg/mL across 24–72 h, with focus on oxidative stress, mitochondrial function, apoptosis, and autophagy.
APS ≤1000 μg/mL was non-cytotoxic under normoxia; at 1000 μg/mL it provided optimal protection against hypoxia-induced cell death, reducing ROS, preserving mitochondrial membrane potential, suppressing HIF-1α accumulation, inhibiting both caspase-dependent and AIF-mediated apoptosis, and enhancing autophagy — with the protective effect strongest at 24–48 h and diminished at 72 h.
- Findings are limited to a single murine photoreceptor cell line (661W); no in vivo validation is presented. - Benefit wanes under prolonged hypoxia (72 h), limiting applicability to chronic retinal ischemia. - Optimal dosing is defined only in cell culture units (μg/mL), with no pharmacokinetic or translational dosing data.
APS shows multi-target cytoprotection in acute photoreceptor hypoxia in vitro, but clinical translation requires in vivo studies; it is not yet applicable to patient care. Clinicians should note the narrow therapeutic window — 2000 μg/mL is toxic even under normoxia.
