NFATc1 Regulation of Dexamethasone-Induced TGFB2 Expression Is Cell Cycle Dependent in Trabecular Meshwork Cells.

Although elevated TGFß2 levels appear to be a causative factor in glaucoma pathogenesis, little is known about how TGFß2 expression is regulated in the trabecular meshwork (TM). Here, we investigated if activation of the cytokine regulator NFATc1 controlled transcription of TGFß2 in human TM cells by using dexamethasone (DEX) to induce NFATc1 activity. The study used both proliferating and cell cycle arrested quiescent cells. Cell cycle arrest was achieved by either cell-cell contact inhibition or serum starvation. ß-catenin staining and p21 and Ki-67 nuclear labeling were used to verify the formation of cell-cell contacts and activity of the cell cycle. NFATc1 inhibitors cyclosporine A (CsA) or 11R-VIVIT were used to determine the role of NFATc1. mRNA levels were determined by RT-qPCR. DEX increased TGFß2 mRNA expression by 3.5-fold in proliferating cells but not in quiescent cells or serum-starved cells, and both CsA and 11R-VIVIT inhibited this increase. In contrast, the expression of other DEX/NFATc1-induced mRNAs (myocilin and ß3 integrin) occurred regardless of the proliferative state of the cells. These studies show that NAFTc1 regulates TGFß2 transcription in TM cells and reveals a previously unknown connection between the TM cell cycle and modulation of gene expression by NFATc1 and/or DEX in TM cells.

Thermomagnetic-Responsive Self-Folding Microgrippers for Improving Minimally Invasive Surgical Techniques and Biopsies.

Traditional open surgery complications are typically due to trauma caused by accessing the procedural site rather than the procedure itself. Minimally invasive surgery allows for fewer complications as microdevices operate through small incisions or natural orifices. However, current minimally invasive tools typically have restricted maneuverability, accessibility, and positional control of microdevices. Thermomagnetic-responsive microgrippers are microscopic multi-fingered devices that respond to temperature changes due to the presence of thermal-responsive polymers. Polymeric devices, made of poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) and polypropylene fumarate (PPF), self-fold due to swelling and contracting of the hydrogel layer. In comparison, soft metallic devices feature a pre-stressed metal bilayer and polymer hinges that soften with increased temperature. Both types of microdevices can self-actuate when exposed to the elevated temperature of a cancerous tumor region, allowing for direct targeting for biopsies. Microgrippers can also be doped to become magnetically responsive, allowing for direction without tethers and the retrieval of microdevices containing excised tissue. The smaller size of stimuli-responsive microgrippers allows for their movement through hard-to-reach areas within the body and the successful extraction of intact cells, RNA and DNA. This review discusses the mechanisms of thermal- and magnetic-responsive microdevices and recent advances in microgripper technology to improve minimally invasive surgical techniques.