Retinal safety and toxicity study of artesunate in vitro and in vivo.

Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5µM was safe for IMG cells in vitro. Both 2.5 and 5 â€‹µM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1ß, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 â€‹µM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 â€‹mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 â€‹µM significantly decreased TNF-α gene expression while ART of 100 â€‹µM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 â€‹µM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.

In depth understanding of retinitis pigmentosa pathogenesis through optical coherence tomography angiography analysis: a narrative review.

Retinitis pigmentosa (RP) is the most recognized inherited retinal disorder involving progressive photoreceptors degeneration which eventually causes blindness. However, the pathogenesis of RP is still unclear, making it difficult to establish satisfying treatments. Evidence have been found to support the theory that vascular dysfunction is associated with the progression of RP. Optical coherence tomography angiography (OCTA) is a newly developed technology that enables visualization as well as quantitative assessment of retinal and choroidal vasculature non-invasively. Advances in OCTA have opened a window for in-depth understanding of RP pathogenesis. Here, we propose a hypothesis of RP pathogenesis based on the current OCTA findings in RP, which includes four stages and two important key factors, vascular dysfunction and microglia activation. Further, we discuss the future animal experiments needed and how advanced OCTA technology can help to further verity the hypothesis. The final goal is to explore potential treatment options with enhanced understanding of RP pathogenesis.

Potential applications of artemisinins in ocular diseases.

Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant (Artemisia annua), which is a traditional Chinese herb that has been universally used as anti-malarial agents for many years. Evidence has accumulated during the past few years which demonstrated the protective effects of artemisinin and its derivatives (artemisinins) in several other diseases beyond malaria, including cancers, autoimmune disorders, inflammatory diseases, viral and other parasite-related infections. Recently, this long-considered anti-malarial agent has been proved to possess anti-oxidant, anti-inflammatory, anti-apoptotic and anti-excitotoxic properties, which make it a potential treatment option for the ocular environment. In this review, we first described the overview of artemisinins, highlighting the activity of artemisinins to other diseases beyond malaria and the mechanisms of these actions. We then emphasized the main points of published results of using artemisinins in targeting ocular disorders, including uveitis, retinoblastoma, retinal neurodegenerative diseases and ocular neovascularization. To conclude, we believe that artemisinins could also be used as a promising therapeutic drug for ocular diseases, especially retinal vascular diseases in the near future.

More than anti-malarial agents: therapeutic potential of artemisinins in neurodegeneration.

Artemisinin, also called qinghaosu, is originally derived from the sweet wormwood plant (Artemisia annua), which is used in traditional Chinese medicine. Artemisinin and its derivatives (artemisinins) have been widely used for many years as anti-malarial agents, with few adverse side effects. Interestingly, evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria, including cancers, inflammatory diseases, and autoimmune disorders. Neurodegeneration is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions, whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders, including Alzheimer's disease. Recently discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation, inflammation, and amyloid beta protein (Aß). In this review, we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities, suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.

Clinical efficacy of integrative therapy in the treatment of non - proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To study the clinical efficacy of integrative therapy in the treatment of non-proliferative diabetic retinopathy.·METHODS: Ninety patients ( 90 eyes ) in our hospital with non - proliferative diabetic retinopathy were randomly divided into three groups. All three groups were treated with diabetes drugs to control blood sugar. The first group was treated with western medicine, the second group was treated with Chinese medicine decoction Traditional Chinese Medicine ( TCM ) treatment, and the third group was treated with the combination of those two methods. All patients were recorded and analyzed changes of clinical effects after 6 courses of treatment.·RESULTS: After 6 courses of treatment, the total efficacy rate of the third group was 86%, markedly higher than that of the first group (57%, P<0. 05) as well as the second group (60%, P<0. 05). The integrative group improved more markedly in terms of vision, macular edema absorption, and ERG b-wave amplitude restoration, the difference being statistically significant (P<0. 05) when compared to the first and the second group.· CONCLUSION: Integrative treatment of diabetic retinopathy could effectively improve the therapeutic effect in patients with non-proliferative retinopathy.

CDC25B mediates rapamycin-induced oncogenic responses in cancer cells.

Because the mammalian target of rapamycin (mTOR) pathway is commonly deregulated in human cancer, mTOR inhibitors, rapamycin and its derivatives, are being actively tested in cancer clinical trials. Clinical updates indicate that the anticancer effect of these drugs is limited, perhaps due to rapamycin-dependent induction of oncogenic cascades by an as yet unclear mechanism. As such, we investigated rapamycin-dependent phosphoproteomics and discovered that 250 phosphosites in 161 cellular proteins were sensitive to rapamycin. Among these, rapamycin regulated four kinases and four phosphatases. A siRNA-dependent screen of these proteins showed that AKT induction by rapamycin was attenuated by depleting cellular CDC25B phosphatase. Rapamycin induces the phosphorylation of CDC25B at Serine375, and mutating this site to Alanine substantially reduced CDC25B phosphatase activity. Additionally, expression of CDC25B (S375A) inhibited the AKT activation by rapamycin, indicating that phosphorylation of CDC25B is critical for CDC25B activity and its ability to transduce rapamycin-induced oncogenic AKT activity. Importantly, we also found that CDC25B depletion in various cancer cell lines enhanced the anticancer effect of rapamycin. Together, using rapamycin phosphoproteomics, we not only advance the global mechanistic understanding of the action of rapamycin but also show that CDC25B may serve as a drug target for improving mTOR-targeted cancer therapies.

Using proteomics and network analysis to elucidate the consequences of synaptic protein oxidation in a PS1 + AbetaPP mouse model of Alzheimer's disease.

Increasing evidence suggests that oxidative injury is involved in the pathogenesis of many age-related neurodegenerative disorders, including Alzheimer's disease (AD). Identifying the protein targets of oxidative stress is critical to determine which proteins may be responsible for the neuronal impairments and subsequent cell death that occurs in AD. In this study, we have applied a high-throughput shotgun proteomic approach to identify the targets of protein carbonylation in both aged and PS1 + AbetaPP transgenic mice. However, because of the inherent difficulties associated with proteomic database searching algorithms, several newly developed bioinformatic tools were implemented to ascertain a probability-based discernment between correct protein assignments and false identifications to improve the accuracy of protein identification. Assigning a probability to each identified peptide/protein allows one to objectively monitor the expression and relative abundance of particular proteins from diverse samples, including tissue from transgenic mice of mixed genetic backgrounds. This robust bioinformatic approach also permits the comparison of proteomic data generated by different laboratories since it is instrument- and database-independent. Applying these statistical models to our initial studies, we detected a total of 117 oxidatively modified (carbonylated) proteins, 59 of which were specifically associated with PS1 + AbetaPP mice. Pathways and network component analyses suggest that there are three major protein networks that could be potentially altered in PS1 + AbetaPP mice as a result of oxidative modifications. These pathways are 1) iNOS-integrin signaling pathway, 2) CRE/CBP transcription regulation and 3) rab-lyst vesicular trafficking. We believe the results of these studies will help establish an initial AD database of oxidatively modified proteins and provide a foundation for the design of future hypothesis driven research in the areas of aging and neurodegeneration.