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Abstract Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease. Graphical Abstract

Steel truss bridges are especially vulnerable in the event of a sudden loss of a load-carrying element, which can trigger a chain of failures. This paper describes a unique case study of a steel truss bridge under construction subjected to sudden member breakages with an extensive monitoring system. The failures occurred during the dismantlement of temporary members that had been used to transform a three-span simply supported steel truss bridge into a three-span continuous structure during incremental launching. These temporary members needed to be removed once the bridge reached its final position. The robustness of the bridge was assessed using computer simulations of various failure scenarios to evaluate its capacity to effectively activate alternative load paths (ALPs). The results demonstrated the structural redundancy of the steel truss bridge. However, the dynamic response resulting from the failure of the temporary upper chord, due to the initially high tension in the rods, should not be overlooked. To mitigate this issue, a structural retrofitting method was proposed, involving jacking the truss girder above the side pier to reduce the tension in the temporary upper chord above the middle pier. The effectiveness of this method was demonstrated through both simulated and formal experimental tests.