Oxidative stress is an imbalance between the increased production of reactive species and reduced antioxidant activity, which can cause a variety of disturbances including ocular diseases. Lycium barbarum polysaccharides (LBPs) are complex polysaccharides isolated from the fruit of L. barbarum, showing distinct roles in antioxidants. Moreover, it is relatively safe and non-toxic. In recent years, the antioxidant activities of LBPs have attracted remarkable attention. In order to illustrate its significance and underlying therapeutic value for vision, we comprehensively review the recent progress on the antioxidant mechanisms of LBP and its potential applications in ocular diseases, including diabetic retinopathy, hypertensive neuroretinopathy, age-related macular degeneration, retinitis pigmentosa, retinal ischemia/reperfusion injury, glaucoma, dry eye syndrome, and diabetic cataract.

Pathological retinal neovascularization (RNV) is the main character of ischemic ocular diseases, which causes severe visual impairments. Though retinal microglia are well acknowledged to play important roles in both physiological and pathological angiogenesis, the molecular mechanisms by which microglia communicates with endothelial cells (EC) remain unknown. In this study, using single-cell RNA sequencing, we revealed that the pro-inflammatory secreted protein Spp1 was the most upregulated gene in microglia in the mouse model of oxygen-induced retinopathy (OIR). Bioinformatic analysis showed that the expression of Spp1 in microglia was respectively regulated via nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor 1α (HIF-1α) pathways, which was further confirmed through in vitro assays using BV2 microglia cell line. To mimic microglia-EC communication, the bEnd.3 endothelial cell line was cultured with conditional medium (CM) from BV2. We found that adding recombinant Spp1 to bEnd.3 as well as treating with hypoxic BV2 CM significantly enhanced EC proliferation and migration, while Spp1 neutralizing blocked those CM-induced effects. Moreover, RNA sequencing of BV2 CM-treated bEnd.3 revealed a significant downregulation of Kit, one of the type III tyrosine kinase receptors that plays a critical role in cell growth and activation. We further revealed that Spp1 increased phosphorylation and expression level of Akt/mTOR signaling cascade, which might account for its pro-angiogenic effects. Finally, we showed that intravitreal injection of Spp1 neutralizing antibody attenuated pathological RNV and improved visual function. Taken together, our work suggests that Spp1 mediates microglia-EC communication in RNV via activating endothelial Kit/Akt/mTOR signaling and is a potential target to treat ischemic ocular diseases.

Microglia is the resident immune cell in the retina, playing the role of immune surveillance in a traditional concept. With the heated focus on the mechanisms of microglia in pathological conditions, more and more functions of microglia have been discovered. Although the regulating role of microglia has been explored in ischemic retinopathy, little is known about its mechanisms in the different stages of the pathological process. Here, we removed microglia in the oxygen-induced retinopathy model by PLX5622 and revealed that the removal of activated microglia reduced pathological angiogenesis in the early stage after ischemic insult and alleviated the over-apoptosis of photoreceptors in the vessel remodeling phase. Our results indicated that microglia might play distinguished functions in the angiogenic and remodeling stages, and that the inhibition of microglia might be a promising target in the future treatment of ischemic retinopathy.