Cytomegalovirus (CMV) is one of the infectious causes of hypertensive anterior uveitis, which is characterized by recurrent episodes of elevated intraocular pressure (IOP) and mild anterior uveitis. Despite the potentially vision-threatening complications of this disease, the underlying mechanisms remain largely undefined. We aimed to investigate whether human trabecular meshwork (TM) cells, the key cell type that regulates IOP, could support CMV replication, as well as demonstrate the relevant pathological changes in TM. When human TM cells were infected with CMV AD169, immediate early antigens were detected 1 day post-infection (dpi); cytopathic changes including rounding, a ballooned appearance with disorganization, and a decreased number of stress fibers were noted in TM cells. The marked increase in viral DNA accumulation was observed most notably at 5 and 7 dpi, suggesting that the active viral infection in human TM cells could be the key mechanism underlying the elevation of IOP in anterior viral uveitis. Notably, CMV infection enhanced the production of transforming growth factor (TGF)-β1, an upstream molecule that increases the resistance of the outflow pathway in human TM cells. The increase of TGF-β1 was countervailed by additional treatment with corticosteroids. Our results provide a pathogenic mechanism for IOP elevation in viral anterior uveitis.
The thermal cycling life of direct bonded aluminum (DBA) and active metal brazing (AMB) substrates with two types of plating—Ni electroplating and Ni–P electroless plating—was evaluated by thermal shock tests between −50 and 250 °C. AMB substrates with Al2O3 and AlN fractured only after 10 cycles, but with Si3N4 ceramic, they retained good thermal stability even beyond 1000 cycles, regardless of the metallization type. The Ni layer on the surviving AMB substrates with Si3N4 was not damaged, while a crack occurred in the Ni–P layer. For DBA substrates, fracture did not occur up to 1000 cycles for all kind of ceramics. On the other hand, the Ni–P layer was roughened and cracked according to the severe deformation of the aluminum layer, while the Ni layer was not damaged after thermal shock tests. In addition, the deformation mechanism of an Al plate on a ceramic substrate was investigated both by microstructural observation and finite element method (FEM) simulation, which confirmed that grain boundary sliding was a key factor in the severe deformation of the Al layer that resulted in the cracking of the Ni–P layer. The fracture suppression in the Ni layer on DBA/AMB substrates can be attributed to its ductility and higher strength compared with those of Ni–P plating.
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