Chen T-C, She P-Y, Chen DF, Lu J-H, Yang C-H, Huang D-S, Chen P-Y, Lu C-Y, Cho K-S, Chen H-F, Su W-F.
Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells. Int J Mol Sci 2019;20(1)
AbstractOptic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.
Chen X, Lei F, Wang L, Xiong X, Song J.
Generation of Tumor Antigen-Specific Cytotoxic T Lymphocytes from Pluripotent Stem Cells. Methods Mol Biol 2019;1884:43-55.
AbstractImmunotherapy is a developing but very promising arsenal to treat cancer. Acquiring a more potent and effective approach in cancer immunotherapy is always the ultimate pursuance. CTL-based therapies are highly acclaimed recently due to its direct killing property. However, difficulty in obtaining adequate number of CTLs is still a major obstacle. In previous studies, it is shown that pluripotent stem cell-derived cytotoxic T lymphocytes (CTL)-especially the genetically engineered tumor antigen-specific CTLs-may serve as a good candidate for this goal. Here we introduce a novel approach in generating tumor antigen-specific CTLs from induced pluripotent stem cells (iPSCs) by using both in vitro and in vivo priming mechanisms for the tumor management in a murine melanoma model.
Costela FM, Saunders DR, Rose DJ, Katjezovic S, Reeves SM, Woods RL.
People With Central Vision Loss Have Difficulty Watching Videos. Invest Ophthalmol Vis Sci 2019;60(1):358-364.
AbstractPurpose: People with central vision loss (CVL) often report difficulties watching video. We objectively evaluated the ability to follow the story (using the information acquisition method). Methods: Subjects with CVL (n = 23) or normal vision (NV, n = 60) described the content of 30-second video clips from movies and documentaries. We derived an objective information acquisition (IA) score for each response using natural-language processing. To test whether the impact of CVL was simply due to reduced resolution, another group of NV subjects (n = 15) described video clips with defocus blur that reduced visual acuity to 20/50 to 20/800. Mixed models included random effects correcting for differences between subjects and between the clips, with age, gender, cognitive status, and education as covariates. Results: Compared to both NV groups, IA scores were worse for the CVL group (P < 0.001). IA reduced with worsening visual acuity (P < 0.001), and the reduction with worsening visual acuity was greater for the CVL group than the NV-defocus group (P = 0.01), which was seen as a greater discrepancy at worse levels of visual acuity. Conclusions: The IA method was able to detect difficulties in following the story experienced by people with CVL. Defocus blur failed to recreate the CVL experience. IA is likely to be useful for evaluations of the effects of vision rehabilitation.
Costela FM, Woods RL.
When Watching Video, Many Saccades Are Curved and Deviate From a Velocity Profile Model. Front Neurosci 2018;12:960.
AbstractCommonly, saccades are thought to be ballistic eye movements, not modified during flight, with a straight path and a well-described velocity profile. However, they do not always follow a straight path and studies of saccade curvature have been reported previously. In a prior study, we developed a real-time, saccade-trajectory prediction algorithm to improve the updating of gaze-contingent displays and found that saccades with a curved path or that deviated from the expected velocity profile were not well fit by our saccade-prediction algorithm (velocity-profile deviation), and thus had larger updating errors than saccades that had a straight path and had a velocity profile that was fit well by the model. Further, we noticed that the curved saccades and saccades with high velocity-profile deviations were more common than we had expected when participants performed a natural-viewing task. Since those saccades caused larger display updating errors, we sought a better understanding of them. Here we examine factors that could affect curvature and velocity profile of saccades using a pool of 218,744 saccades from 71 participants watching "Hollywood" video clips. Those factors included characteristics of the participants (e.g., age), of the videos (importance of faces for following the story, genre), of the saccade (e.g., magnitude, direction), time during the session (e.g., fatigue) and presence and timing of scene cuts. While viewing the video clips, saccades were most likely horizontal or vertical over oblique. Measured curvature and velocity-profile deviation had continuous, skewed frequency distributions. We used mixed-effects regression models that included cubic terms and found a complex relationship between curvature, velocity-profile deviation and saccade duration (or magnitude). Curvature and velocity-profile deviation were related to some video-dependent features such as lighting, face presence, or nature and human figure content. Time during the session was a predictor for velocity profile deviations. Further, we found a relationship for saccades that were in flight at the time of a scene cut to have higher velocity-profile deviations and lower curvature in univariable models. Saccades characteristics vary with a variety of factors, which suggests complex interactions between oculomotor control and scene content that could be explored further.