Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of β-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.
As a member of the transition metal nitride material family, titanium nitride (TiN) quantum dots (QDs) have attracted great attention in optical and electronic fields because of their excellent optoelectronic properties and favorable stability. Herein, TiN QDs were synthesized and served as a saturable absorber (SA) for an ultrafast fiber laser. Due to the strong nonlinear optical absorption characteristics with a modulation depth of ~33%, the typical fundamental mode-locked pulses and harmonics mode-locked pulses can be easily obtained in an ultrafast erbium-doped fiber laser with a TiN-QD SA. In addition, at the maximum pump power, harmonic mode-locked pulses with a repetition rate of ~1 GHz (164th order) and a pulse duration of ~1.45 ps are achieved. As far as we know, the repetition rate is the highest in the ultrafast fiber laser using TiN QDs as an SA. Thus, these experimental results indicate that TiN QDs can be considered a promising material, showing more potential in the category of ultrafast laser and nonlinear optics.
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