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Author(s): Tomoya Fukawa [1, 2, 3]; Benjamin Chua Yan-Jiang [4]; Jason Chua Min-Wen [4]; Elwin Tan Jun-Hao [4]; Dan Huang [2]; Chao-Nan Qian [5]; Pauline Ong [1, 2]; Zhimei Li [...]

Targeting the oxidative stress response has recently emerged as a promising strategy for the development of therapeutic drugs for a broad spectrum of diseases. Supporting this strategy, we have reported that chitosan nanoparticles synthesized with a controlled size had selective cytotoxicity in leukemia cells through the mechanism related to reactive oxygen species (ROS) generation. Herein, we found that the cellular uptake of chitosan nanoparticles was enhanced in a time dependent manner and inhibited the cellular proliferation of leukemia cells in a dose dependent manner with elevation of the reactive oxygen species (ROS) showing a stronger effect on apoptosis, associated with the upregulation of caspase activity and the depletion of reduced glutathione. Propidium iodide and calcein staining demonstrated the central role of the chitosan nanoparticles in triggering elevated ROS, inducing cell death and intracellular oxidative activity. The enhanced free radical scavenging activity of the chitosan nanoparticles further iterates its antioxidant activity. In vitro quantitative phase imaging studies at the single cell level further demonstrated the inhibition of cellular proliferation with significant changes in cellular behavior and this supported our hypothesis. Hemocompatibility tests demonstrated that chitosan nanoparticles could be used safely for in vivo applications. Our findings suggest that chitosan nanoparticles may be a promising redox active candidate for therapeutic applications. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of changing heart rate on the ocular pulse and the dynamic biomechanical behavior of the optic nerve head (ONH) using a comprehensive mathematical model., Methods: In a finite element model of a healthy eye, a biphasic choroid consisted of a solid phase with connective tissues and a fluid phase with blood, and the lamina cribrosa (LC) was viscoelastic as characterized by a stress-relaxation test. We applied arterial pressures at 18 ocular entry sites (posterior ciliary arteries), and venous pressures at four exit sites (vortex veins). In the model, the heart rate was varied from 60 to 120 bpm (increment: 20 bpm). We assessed the ocular pulse amplitude (OPA), pulse volume, ONH deformations, and the dynamic modulus of the LC at different heart rates., Results: With an increasing heart rate, the OPA decreased by 0.04 mm Hg for every 10 bpm increase in heart rate. The ocular pulse volume decreased linearly by 0.13 µL for every 10 bpm increase in heart rate. The storage modulus and the loss modulus of the LC increased by 0.014 and 0.04 MPa, respectively, for every 10 bpm increase in heart rate., Conclusions: In our model, the OPA, pulse volume, and ONH deformations decreased with an increasing heart rate, whereas the LC became stiffer. The effects of blood pressure/heart rate changes on ONH stiffening may be of interest for glaucoma pathology.