Effects of peptide ratios in nanofibre-based hydrogels for the prevention of capsular opacification

PurposeTo moderate the capsular opacification (CO) response after lens surgery, an experimental study was performed in which nanofibre-based hydrogels (nanogels) with different ratios of attached peptides were applied to provide extracellular matrix-related cues for lens epithelial cells (LECs) in a porcine eye model. MethodsThe lens content was removed, and the capsules were refilled with nanogel. Lenses were divided into two groups, the first group (n=34) was refilled with nanogels containing different ratios of two laminin-derived peptides (IKVAV+YIGSR), and the latter group (n=26) was refilled with nanogel combinations of a fibronectin-derived and a type IV collagen-derived peptide (RGDS+DGEA). Two lenses were refilled with culture medium to investigate the effect of the medium on LECs. After refilling, lenses were extracted and cultured for 3weeks. Lens epithelial cells (LECs) were assessed for morphology and alpha-smooth muscle actin (SMA) expression using confocal laser scanning microscopy. ResultsDifferences were seen in cell morphology between lenses refilled with nanogels with IKVAV+YIGSR and RGDS+DGEA peptides. In nanogels with IKVAV+YIGSR peptides, differences in LEC morphology were largest when ratios between the peptides were unequal, whereas LEC responses from the RGDS+DGEA refilled groups showed variation in LEC morphology dependent on the total quantity of mixed-in peptides. The culture medium did not induce proliferation or transformation of LECs. ConclusionsRatios and concentrations of cell adhesion-mediating peptides both can direct the LEC response, depending on the adhesion molecules of origin, by influencing LEC proliferation and transformation. Nanogels with incorporated peptides may be tuned towards CO prevention

Emerging mechanisms and novel applications of hydrogen gas therapy

Clinical and pre-clinical studies have reported a broad range of applications for hydrogen gas therapy. Classically, conventional antioxidant therapy is limited because it neutralizes both the detrimental and protective effects of reactive oxygen species. As a weak reducing agent, hydrogen gas avoids this paradox by reacting with strong oxidants while leaving other beneficial oxidants reactive. This review gathers a promising list of hydrogen gas applications that merit further mechanistic investigation and additional therapeutic trials. Reports support the ability of hydrogen gas to downregulate the expression of pro-inflammatory cytokines and pro-apoptotic factors. Mechanistically, hydrogen gas has been shown to downregulate miR-9 and miR-21, while upregulating miR-199 to reduce inflammatory injury. In angiogenic pathways, hydrogen’s inhibition of cyclic guanosine monophosphate-degrading phosphodiesterase led to higher levels of cyclic guanosine monophosphate, activation of protein kinase, and angiogenesis; next, as hydrogen gas increased the levels of intracellular calcium, stimulated vascular endothelial growth factor increased nitric oxide production. In conjunction, hydrogen gas opened adenosine triphosphate-sensitive potassium channel channels, which activate downstream mitogen-activated protein kinase pathways. Growing molecular mechanisms have discovered a plethora of downstream targets for hydrogen gas therapy that include autophagy (via the adenosine 5’-monophosphate-activated protein kinase/mammalian target of rapamycin pathway), histone modification, mitochondrial unfolded protein response, acute oxidative stress after exercise, and oxidative stress secondary to aging. In conclusion, evolving research has discovered novel molecular connections that will continue to widen applications for hydrogen therapy