Myosin 1f-mediated activation of microglia contributes to the photoreceptor degeneration in a mouse model of retinal detachment.

Photoreceptor death and neurodegeneration is the leading cause of irreversible vision loss. The inflammatory response of microglia plays an important role in the process of neurodegeneration. In this study, we chose retinal detachment as the model of photoreceptor degeneration. We found Myosin 1f was upregulated after retinal detachment, and it was specifically expressed in microglia. Deficiency of myosin 1f protected against photoreceptor apoptosis by inhibiting microglia activation. The elimination of microglia can abolish the protective effect of myosin 1f deficiency. After stimulation by LPS, microglia with myosin 1f deficiency showed downregulation of the MAPK and AKT pathways. Our results demonstrated that myosin 1f plays a crucial role in microglia-induced neuroinflammation after retinal injury and photoreceptor degeneration by regulating two classic inflammatory pathways and thereby decreasing the expression of inflammatory cytokines. Knockout of myosin 1f reduces the intensity of the immune response and prevents cell death of photoreceptor, suggesting that myosin 1f can be inhibited to prevent a decline in visual acuity after retinal detachment.

An investigation of traffic density changes inside Wuhan during the COVID-19 epidemic with GF-2 time-series images.

In order to mitigate the spread of COVID-19, Wuhan was the first city to implement strict lockdown policy in 2020. Even though numerous researches have discussed the travel restriction between cities and provinces, few studies focus on the effect of transportation control inside the city due to the lack of the measurement and available data in Wuhan. Since the public transports have been shut down in the beginning of city lockdown, the change of traffic density is a good indicator to reflect the intracity population flow. Therefore, in this paper, we collected time-series high-resolution remote sensing images with the resolution of 1 m acquired before, during and after Wuhan lockdown by GF-2 satellite. Vehicles on the road were extracted and counted for the statistics of traffic density to reflect the changes of human transmissions in the whole period of Wuhan lockdown. Open Street Map was used to obtain observation road surfaces, and a vehicle detection method combing morphology filter and deep learning was utilized to extract vehicles with the accuracy of 62.56%. According to the experimental results, the traffic density of Wuhan dropped with the percentage higher than 80%, and even higher than 90% on main roads during city lockdown; after lockdown lift, the traffic density recovered to the normal rate. Traffic density distributions also show the obvious reduction and increase throughout the whole study area. The significant reduction and recovery of traffic density indicates that the lockdown policy in Wuhan show effectiveness in controlling human transmission inside the city, and the city returned to normal after lockdown lift.

xCT regulates redox homeostasis and promotes photoreceptor survival after retinal detachment.

BACKGROUNDS: Photoreceptor degeneration underlies various retinal disorders that lead to vision impairment. Currently, no effective medication is available to rescue photoreceptors under disease conditions. Elucidation of the molecular pathways involved in photoreceptor degeneration is a prerequisite for the rational design of therapeutic interventions. Photoreceptors are among the most energy-demanding tissues that require highly active oxidative phosphorylation. Therefore, disruption of metabolic support to photoreceptors results in a redox imbalance and subsequent cell death. We hypothesize that the redox regulatory pathway could be a potential therapeutic target to rescue photoreceptors under disease conditions. METHODS: Experimental retinal detachment was induced in mice. A murine photoreceptor-derived 661w cell line treated with H2O2 was employed as an in vitro model to study the cellular response to oxidative stress. The expression and functional role of xCT, an upstream regulator of redox homeostasis, was assessed in vivo and in vitro. An xCT expression vector was constructed for an in vivo study to evaluate the therapeutic potential of this molecule. RESULTS: xCT expression was upregulated in detached retina and H2O2-stimulated 661w cells compared to the control cells. Pharmacological inhibition of xCT by sulfasalazine (SAS) promoted photoreceptor degeneration after retinal detachment and 661w cell death upon H2O2 treatment. Additionally, SAS treatment induced reactive oxidative species (ROS) accumulation, glutathione (GSH) depletion, and glutamate release in 661w cells. In contrast, xCT overexpression via viral infection protected photoreceptors from degeneration after retinal detachment. CONCLUSION: We conclude that xCT expression is upregulated in photoreceptors after retinal detachment and plays a neuroprotective role in preserving photoreceptors. Mechanistically, xCT promotes cellular homeostasis by regulating intracellular ROS and GSH levels, which are critical to photoreceptor survival after retinal detachment. Collectively, our findings identify xCT as a potential therapeutic target for protection of photoreceptors under disease conditions.

An improved method for establishment of murine retinal detachment model and its 3D vascular evaluation.

Retinal detachment (RD) results in disruption of retinal physiology and visual function. Although surgical intervention has been well-developed to restore the retinal anatomic structure, post-op progression of visual function decline is prominent in a large proportion of patients. Therefore, the establishment of a disease model that accurately mimics RD pathogenesis is crucial to mechanistic study and drug screening. General protocols to induce RD in mice are frequently associated with complications leading to model instability and reduced reproducibility. In this study, we established a stable and reproducible mice RD model with a detached area of over 90% and rare complications. Briefly, the modified method was realized by vitreous humor extraction to reduce intraocular pressure, followed by directly-visible hyaluronic acid injection into subretinal space. The detachment of retina was confirmed by fundus photography, and progressive thinning of the outer nuclear layer (ONL) was determined by HE staining. Apoptotic signals were prominent in the ONL. Consistently, visual function was significantly compromised as determined by ERG. Moreover, retinal vasculature appeared to remodel and acquired winding, twisted and dilated structures illustrated by 3D reconstruction. In addition, activation of Müller cells and microglia, and infiltration of blood-derived macrophages were detected locally. Collectively, we have established a modified protocol to model RD with increased stability, reproducibility and fewer complications, and 3D high-resolution imaging and reconstruction of vasculature could provide new tools to evaluate this model.