Loss of photoreceptors is the central pathology accountable for irreversible vision impairment in patients with photoreceptor degenerative disorders. Currently, mechanisms-based pharmacological therapies protecting photoreceptors from degenerative progression remain clinically unavailable. Photooxidative stress plays a pivotal role in initiating the degenerative cascade in photoreceptors. Meanwhile, photoreceptor degeneration interacts closely with neurotoxic inflammatory responses primarily mediated by aberrantly activated microglia in the retina. Thus, therapies with anti-oxidant and anti-inflammatory properties have been actively investigated for their pharmacological value in controlling photoreceptor degeneration. In the current study, we examined the pharmacological potentials of ginsenoside Re (Re), a naturally occurring antioxidant with anti-inflammatory activities, in photooxidative stress-mediated photoreceptor degeneration. Our results demonstrate that Re attenuates photooxidative stress and associated lipid peroxidation in the retina. Furthermore, Re treatment preserves the morphological and functional integrity of the retina, counteracts photooxidative stress-induced perturbation of the retinal gene expression profiles and mitigates photoreceptor degeneration-associated neuroinflammatory responses and microglia activation in the retina. Lastly, Re partially antagonizes the deleterious effects of photooxidative stress on müller cells, verifying its beneficial impact on retina homeostasis. In conclusion, the work here provides experimental evidence supporting novel pharmacological implications of Re in attenuating photooxidative stress-mediated photoreceptor degeneration and ensuing neuroinflammation.

光感受器丧失是导致光感受器退行性疾病患者出现不可逆视力损害的主要病理原因。目前，基于机制的保护光感受器免于退行性进展的药物疗法在临床上仍然无法实现。光氧化应激在启动光感受器退行性级联中起着关键作用。同时，光感受器变性与主要由视网膜中异常激活的小胶质细胞介导的神经毒性炎症反应密切相关。因此，人们正在积极研究具有抗氧化和抗炎特性的疗法在控制光感受器变性方面的药理学价值。在当前的研究中，我们研究了人参皂苷 Re (Re)（一种具有抗炎活性的天然抗氧化剂）在光氧化应激介导的光感受器变性中的药理学潜力。我们的结果表明，Re 可减轻视网膜中的光氧化应激和相关的脂质过氧化。此外，Re治疗可以保留视网膜的形态和功能完整性，抵消光氧化应激引起的视网膜基因表达谱的扰动，并减轻视网膜中光感受器变性相关的神经炎症反应和小胶质细胞活化。最后，Re 部分拮抗光氧化应激对米勒细胞的有害影响，验证了其对视网膜稳态的有益影响。总之，这项工作提供了实验证据，支持 Re 在减轻光氧化应激介导的光感受器变性和随后的神经炎症方面的新药理学意义。