A revisit of rod microglia in preclinical studies

Microglial cells（or microglia）are the mononuclear phagocytes residing in the central nervous system（CNS）.In homeostasis,they showed ramified morphology with relative small cell bodies and long processes（Figure 1A）.They detect injury signals in the CNS and get activated.

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 antiinflammation,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 5μM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1β,IL-6,TNF-α,and Arg-1.In the in vivo study,intravitreal injection of ART below 100μM did not cause deterioration in the retinal function and RGC survival of the mouse eyes,while 1 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 100μM significantly decreased TNF-αgene expression while ART of 100μM significantly increased IL-10 in the mouse retina.Conclusions:Intravitreal injection of 100μM ART could downregulate TNF-αwhile 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.