Cells under cyclic stretch sense their environments and induce responses such as actin stress fiber (SF) reorientation and morphological changes. These physiological responses are thought to occur when cells sense incompatibility between SF orientation and stretching direction. This hypothesis requires existence of SFs. However, such existence of SFs in cells under cyclic stretch remains unclear since few studies attempted to track the existence of SFs throughout cyclic stretch. In order to track the existence of SFs throughout cyclic stretch, high time resolution time-lapse imaging was improved in two points. First, SFs were clearly imaged with coexpression of DsRed-zyxin and GFP-actin. Second, time resolution was improved so that fluorescence images were obtained every 28 sec. With the improved high time resolution time-lapse imaging, it was revealed, for the first time, that SFs could exist continuously throughout cyclic stretch. Moreover, physiological responses including morphological change as well as SF reorientation occurred during the time when SFs formed incompatibility between SF orientation and stretching direction. These results demonstrated that SFs continuously existed in cells under cyclic stretch and in turn suggested that continuous presence of incompatibility between orientation of long-lasting SFs and the stretching direction might be important for mechanosensing which induces physiological responses.

Background Filamentous fungi are ubiquitous in plants, water, and soil. The predominant fungi that infect the human cornea include Fusarium and Aspergillus species. The onset of fungal endophthalmitis is indolent, and typically takes weeks to months to develop after corneal infection. We report a case of Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during intravenous tocilizumab therapy. Case presentation A 65-year-old female patient was referred to our department due to pain and decreased vision in her left eye. Slit-lamp examination showed a white focus on the upper peripheral cornea, hypopyon, anterior chamber fibrin formation, marked ciliary hyperemia, and whole corneal epithelial defects. As the corneal scraping smear was positive for filamentous fungi and Fusarium species were detected by aqueous humor polymerase chain reaction, anti-fungal therapy was started. Although the initial response to anti-fungal therapy was good, we observed corneal infiltration, worsening hypopyon, and vitreous opacity after tocilizumab infusion. Given that the infection continued to progress despite conservative therapy, we performed penetrating keratoplasty combined with vitrectomy. After removal of the white focus beneath the intraocular lens, a temporary corneal prosthesis was mounted and the dense vitreous opacity was removed. Finally, a frozen donor graft was sutured in place. The corneal infiltration, hypopyon, and vitreous opacity all disappeared after the operation. Conclusion The rapid progression of Fusarium keratitis to endophthalmitis in a patient who was receiving a regular infusion of tocilizumab demonstrates that ocular condition should be closely monitored during systemic tocilizumab administration due to increased risk of infection.

Adherent cells generate traction forces, which are generated by and transmitted along the actin cytoskeleton to the underlying external substrate via focal adhesions. These cell generated forces are fundamental for maintaining cell shape and driving cell migration as well as triggering signaling pathways to promote processes such as differentiation and proliferation. Here we investigate how mechanical stretch affects traction forces. Following moderate mechanical stretching and release, traction forces are increased and then return to basal levels. However, when cells are stretched with relatively large strains, >10%, traction forces fail to return to basal levels and are attenuated. In this study, we investigate whether cells experiencing attenuated traction forces, following a large strain, can still respond to subsequent mechanical stretching. Traction forces were measured in cells following a consecutive 12% increase in mechanical stretch. We show that, even after traction force attenuation occurs, cells are able to respond to consecutive mechanical stretching by increasing traction force. Visualization of stress fibers, with GFP-actin, indicates that the attenuation of traction force is accompanied by a decrease in stress fiber integrity during mechanical stretching. The ability of cells to increase traction force during a second round of stretching, following attenuation, maybe generated by intact stress fibers that escape damage.

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