Development of a Non-Contacting Muscular Activity Measurement System for Evaluating Knee Extensors Training in Real-Time.

To give people more specific information on the quality of their daily motion, it is necessary to continuously measure muscular activity during everyday occupations in an easy way. The traditional methods to measure muscle activity using a combination of surface electromyography (sEMG) sensors and optical motion capture system are expensive and not suitable for non-technical users and unstructured environment. For this reason, in our group we are researching methods to estimate leg muscle activity using non-contact wearable sensors, improving ease of movement and system usability. In a previous study, we developed a method to estimate muscle activity via only a single inertial measurement unit (IMU) on the shank. In this study, we describe a method to estimate muscle activity during walking via two IMU sensors, using an original sensing system and specifically developed estimation algorithms based on ANN techniques. The muscle activity estimation results, estimated by the proposed algorithm after optimization, showed a relatively high estimation accuracy with a correlation efficient of R2 = 0.48 and a standard deviation STD = 0.10, with a total system average delay of 192 ms. As the average interval between different gait phases in human gait is 250-1000 ms, a 192 ms delay is still acceptable for daily walking requirements. For this reason, compared with the previous study, the newly proposed system presents a higher accuracy and is better suitable for real-time leg muscle activity estimation during walking.

Comparison of clinical outcomes of 2 platforms for topography-guided LASIK in primary eyes.

PURPOSE: To compare differences in visual, refractive, and ablating outcomes between corneal topography-guided laser in situ keratomileusis (LASIK) by SCHWIND AMARIS and WaveLight Contoura for myopia and myopic astigmatism correction. SETTING: Department of Refractive Surgery, Guangzhou Aier Eye Hospital, Guangzhou, China. DESIGN: Prospective nonrandomized study. METHODS: Patients treated with LASIK to correct ametropia and corneal higher-order aberrations (HOAs) with 6.5 mm of plan optical zone were recruited. In the AMARIS platform, there were 2 centration strategies: the symmetric (AA) and asymmetric (AS) offset modes. In the WaveLight platform, there was only symmetric offset (ES) mode. HOAs, contrast sensitivity, effective optical zone (EOZ), ablation depth, and ablating center were evaluated 3 months after the operation. RESULTS: The study included 138 eyes. At 3 months after operation, the postoperative manifest refractive spherical equivalent was 0.04 ± 0.34 diopters (D), 0.06 ± 0.25 D, and -0.09 ± 0.21 D in AS, AA, and ES groups, respectively (P = .018). The EOZs of the AS and AA groups were 5.01 mm and 4.96 mm, and both were larger than 4.88 mm in the ES group (P = .04 and .03, respectively). The ablation depth of the AS group was 103.6 µm, which were larger than 86.6 µm in the AA group and 91.2 µm in the ES group. CONCLUSIONS: The SCHWIND AMARIS and WaveLight EX500 corneal topography-guided LASIK achieved comparable and excellent visual and refractive outcomes. The EX500 Contoura LASIK ablated less corneal tissue because of the smaller EOZ compared with the AMARIS, with a similar plan optical zone.

Establishment of a Rapid Lesion-Controllable Retinal Degeneration Monkey Model for Preclinical Stem Cell Therapy.

BACKGROUND: Retinal degenerative disorders (RDs) are the main cause of blindness without curable treatment. Our previous studies have demonstrated that human-induced pluripotent stem cells can differentiate into retinal organoids with all subtypes of retina, which provides huge promise for treating these diseases. Before these methods can be realized, RD animal models are required to evaluate the safety and efficacy of stem cell therapy and to develop the surgical tools and procedures for cell transplantation in patients. This study involved the development of a monkey model of RD with controllable lesion sites, which can be rapidly prepared for the study of preclinical stem cell therapy among other applications. METHODS: Sodium nitroprusside (SNP) in three doses was delivered into the monkey eye by subretinal injection (SI), and normal saline was applied as control. Structural and functional changes of the retinas were evaluated via multimodal imaging techniques and multifocal electroretinography (mfERG) before and after the treatment. Histological examination was performed to identify the target layer of the affected retina. The health status of monkeys was monitored during the experiment. RESULTS: Well-defined lesions with various degrees of retinal degeneration were induced at the posterior pole of retina as early as 7 days after SNP SI. The damage of SNP was dose dependent. In general, 0.05 mM SNP caused mild structural changes in the retina; 0.1 mM SNP led to the loss of outer retinal layers, including the outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE); while 0.2 mM SNP impacted the entire layer of the retina and choroid. MfERG showed reduced amplitude in the damaged region. The structural and functional damages were not recovered at 7-month follow-up. CONCLUSION: A rapidly induced lesion site-controllable retinal degeneration monkey model was established by the subretinal administration of SNP, of which the optimal dose is 0.1 mM. This monkey model mimics the histological changes of advanced RDs and provides a valuable platform for preclinical assessment of stem cell therapy for RDs.

Self-Formation of RPE Spheroids Facilitates Enrichment and Expansion of hiPSC-Derived RPE Generated on Retinal Organoid Induction Platform.

Purpose: Retinal pigment epithelium (RPE) and neural retina could be generated concurrently through retinal organoid induction approaches using human induced pluripotent stem cells (hiPSCs), providing valuable sources for cell therapy of retinal degenerations. This study aims to enrich and expand hiPSC-RPE acquired with this platform and explore characteristics of serially passaged RPE cells. Methods: RPE has been differentiated from hiPSCs with a published retinal organoid induction method. After detachment of neural retina on the 4th week, the remaining mixture was scraped from the dish and subjected to suspension culture for the formation of RPE spheroids. RPE sheets were isolated and digested for expansion. The cellular, molecular, and functional features of expanded RPE cells were evaluated by different assays. Results: Under suspension culture, hiPSC-RPE spheroids with pigmentation self-formed were readily enriched by removing the non-retinal tissues. RPE sheets were further dissected and purified from the spheroids. The individualized RPE cells could be passaged every week for at least 5 times in serum medium, yielding large numbers of cells with high quality in a short period. In addition, when switched to a serum-free medium, the passaged RPE cells could mature in cellular, molecular, and physiological levels, including repigmentation, markers expression, and phagocytosis. Conclusions: We developed a simple and novel RPE spheroids formation approach to enrich and expand hiPSC-RPE cells generated along with retinal neurons on a universal retinal organoid induction platform. This achievement will reduce the cost and time in producing retinal cells for basic and translational researches, in particular for retinal cell therapy.

Generation of Retinal Organoids with Mature Rods and Cones from Urine-Derived Human Induced Pluripotent Stem Cells.

Urine cells, a body trash, have been successfully reprogrammed into human induced pluripotent stem cells (U-hiPSCs) which hold a huge promise in regenerative medicine. However, it is unknown whether or to what extent U-hiPSCs can generate retinal cells so far. With a modified retinal differentiation protocol without addition of retinoic acid (RA), our study revealed that U-hiPSCs were able to differentiate towards retinal fates and form 3D retinal organoids containing laminated neural retina with all retinal cell types located in proper layer as in vivo. More importantly, U-hiPSCs generated highly mature photoreceptors with all subtypes, even red/green cone-rich photoreceptors. Our data indicated that a supplement of RA to culture medium was not necessary for maturation and specification of U-hiPSC-derived photoreceptors at least in the niche of retinal organoids. The success of retinal differentiation with U-hiPSCs provides many opportunities in cell therapy, disease modeling, and drug screening, especially in personalized medicine of retinal diseases since urine cells can be noninvasively collected from patients and their relatives.

Generation of an acute retinal photoreceptor degeneration model in rabbits.

PURPOSE: To assess the appropriate dose of sodium nitroprusside for establishing acute retinal photoreceptor degeneration models in rabbits. METHODS: Sodium nitroprusside (SNP) was delivered intravitreously. Sixteen New Zealand White rabbits are divided into four groups randomly: 0.1 mM, 0.25 mM, 0.5 mM SNP intravitreal injection group (experimental groups), and normal saline intravitreal injection group (control group). Assessments included weight, anterior segment photography, fundus photography, Hematoxylin-eosin staining, immunofluorescence, multi-focal electroretinogram (mfERG) and pupillary direct light reflex were performed at baseline and day 28 after injection. The spectral domain optical coherence tomography (SD-OCT) and full field electroretinogram (fERG) were performed at baseline and day 1, 3, 7, 14, 21 and 28 after injection. RESULTS: No complications and no significant different in weight were found among all groups. No obvious change was found by slit lamp and fundus photography after injection in all groups. In SD-OCT exams, a time-dependent and dose-dependent injury of photoreceptor was found in SNP injection groups (P<0.05). The thickness of inner nuclear and plexiform layer was significantly decreased in 0.5 mM group. HE staining and immunofluorescence present the photoreceptor damage at the posterior pole (0.1, 0.25, 0.5 mM groups) and periphery (0.5 mM group). fERG and mfERG showed significant dose-dependent responses depression in SNP injection groups (P<0.05). The pupillary direct light reflex in SNP groups declined significantly at day 28th than pre-injection (P<0.05). CONCLUSIONS: Sodium nitroprusside of 0.1 mM and 0.25 mM can lead to monolayer photoreceptor degeneration at posterior pole in rabbits and the lesion is stable at 1 month after SNP injection.