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Extracellular vesicles and nanoparticles (EVPs) are now recognized as a novel form of cell–cell communication. All cells release a wide array of heterogeneous EVPs with distinct protein, lipid, and RNA content, dependent on the pathophysiological state of the donor cell. The overall cargo content in EVPs is not equivalent to cellular levels, implying a regulated pathway for selection and export. In cancer, release and uptake of EVPs within the tumour microenvironment can influence growth, proliferation, invasiveness, and immune evasion. Secreted EVPs can also have distant, systemic effects that can promote metastasis. Here, we review current knowledge of EVP biogenesis and cargo selection with a focus on the role that extracellular RNA plays in oncogenesis and metastasis. Almost all subtypes of RNA have been identified in EVPs, with miRNAs being the best characterized. We review the roles of specific miRNAs that have been detected in EVPs and that play a role in oncogenesis and metastasis.

Abstract This study presents a novel training technique, visual + electrotactile proprioception training (visual + EP training), which provides additional proprioceptive information via tactile channel during motor training to enhance the training effectiveness. In this study, electrotactile proprioception delivers finger aperture distance information in real-time, by mapping frequency of electrical stimulation to finger aperture distance. To test the effect of visual + EP training, twenty-four healthy subjects participated in the experiment of matching finger aperture distance with distance displayed on screen. Subjects were divided to three groups: the first group received visual training and the other two groups received visual + EP training with or without a post-training test with electrotactile proprioception. Finger aperture control error was measured before and after the training (baseline, 15-min post, 24-h post). Experimental data suggest that both training methods decreased finger aperture control error at 15-min post-training. However, at 24-h post-training, the training effect was fully retained only for the subjects who received visual + EP training, while it washed out for the subjects with visual training. Distribution analyses based on Bayesian inference suggest that the most likely mechanism of this long-term retention is proprioceptive recalibration. Such applications of artificially administered sense have the potential to improve motor control accuracy in a variety of applications.

Abstract 5‐Fluorouracil (5‐FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5‐FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5‐FU on post‐transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell‐cell communication. We found that treatment of colorectal cancer (CRC) cells with 5‐FU represses sEV export of miRNA and snRNA‐derived RNAs, but promotes export of snoRNA‐derived RNAs. Strikingly, 5‐FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5‐FU exposure led to increased levels of cellular small RNAs containing a variety of methyl‐modified bases. These unexpected findings show that 5‐FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs.

ABSTRACT The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others.

Sensory feedback provides critical interactive information for the effective use of hand prostheses. Non-invasive neural interfaces allow convenient access to the sensory system, but they communicate a limited amount of sensory information. This study examined a novel approach that leverages a direct and natural sensory afferent pathway, and enables an evoked tactile sensation (ETS) of multiple digits in the projected finger map (PFM) of participants with forearm amputation non-invasively. A bidirectional prosthetic interface was constructed by integrating the non-invasive ETS-based feedback system into a commercial prosthetic hand. The pressure information of five fingers was encoded linearly by the pulse width modulation range of the buzz sensation. We showed that simultaneous perception of multiple digits allowed participants with forearm amputation to identify object length and compliance by using information about contact patterns and force intensity. The ETS enhanced the grasp-and-transport performance of participants with and without prior experience of prosthetic use. The functional test of transport-and-identification further revealed improved execution in classifying object size and compliance using ETS-based feedback. Results demonstrated that the ETS is capable of communicating somatotopically compatible information to participants efficiently, and improves sensory discrimination and closed-loop prosthetic control. This non-invasive sensory interface may establish a viable way to restore sensory ability for prosthetic users who experience the phenomenon of PFM.

Abstract Background Analysis of tongue movement would benefit from a reference showcasing healthy tongue capability. We aimed to develop a reference of tongue capability and evaluated the role of visual feedback on the expression of movement. Methods Using a wireless tracking intraoral wearable device, we composed probability distributions of the tongue tip as subjects were asked to explore the entire sensing surface area. Half of the 32 subjects received live visual feedback of the location of the center of the tongue tip contact. Results We observed that the visual feedback group was 51.0% more consistent with each other in the position domain, explored 21.5% more sensing surface area, and was 50.7% more uniformly distributed. We found less consistent results when we evaluated velocity and acceleration. Conclusion Visual feedback best established a healthy capability reference which can be used for designing new interfaces, quantifying tongue ability, developing new diagnostic and rehabilitation techniques, and studying underlying mechanisms of tongue motor control.

In metazoans, microRNAs (miRNAs) are essential regulators of gene expression, affecting critical cellular processes from differentiation and proliferation, to homeostasis. During miRNA biogenesis, the miRNA strand that loads onto the RNA-induced Silencing Complex (RISC) can vary, leading to changes in gene targeting and modulation of biological pathways. To investigate the impact of these “arm switching” events on gene regulation, we analyzed a diverse range of tissues and developmental stages in zebrafish by comparing 5p and 3p arms accumulation dynamics between embryonic developmental stages, adult tissues, and sexes. We also compared variable arm usage patterns observed in zebrafish to other vertebrates including arm switching data from fish, birds, and mammals. Our comprehensive analysis revealed that variable arm usage events predominantly take place during embryonic development. It is also noteworthy that isomiR occurrence correlates to changes in arm selection evidencing an important role of microRNA distinct isoforms in reinforcing and modifying gene regulation by promoting dynamics switches on miRNA 5p and 3p arms accumulation. Our results shed new light on the emergence and coordination of gene expression regulation and pave the way for future investigations in this field.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology of CIPN is not completely understood; however, it is believed that chemotherapies induce peripheral neuropathy via directly damaging mitochondria, impairing the function of ion channels, triggering immunological mechanisms, and disrupting microtubules. The treatment of CIPN is a medical challenge, and there are no approved pharmacological options. Currently, duloxetine and other antidepressants, antioxidant, anti-inflammatory, and ion-channel targeted therapies are commonly used in clinics to relieve the symptoms of CIPN. Several other types of drugs, such as cannabinoids, sigma−1 receptor antagonists, and nicotinamides ribose, are being evaluated in preclinical and clinical studies. This paper summarizes the information related to the physiology of CIPN and medicines that could be used for treating this condition.

Abstract Background Robotic-assisted unicompartmental knee arthroplasty (UKA) improves implant accuracy, however whether this translates to patient function is less clear. Various outcomes have been reported but muscle recovery has not been previously investigated. Objective To explore sequential change in lower limb muscle strength following robotic-assisted UKA with isokinetic dynamometry. Results 12 participants undergoing rUKA for medial compartment osteoarthritis were assessed pre-operatively, and at 6- and 12-weeks post-operatively. Maximal muscle strength changed over time in both quadriceps (p = 0.006) and hamstrings (p = 0.018) muscle groups. Quadriceps strength reduced from 88.52(39.86)Nm to 74.47(27.58)Nm by 6-weeks (p = 0.026), and then recovered to 90.41(38.76)Nm by 12-weeks (p = 0.018). Hamstring strength reduced from 62.45(23.18)Nm to 54.12(20.49)Nm by 6-weeks (p = 0.016), and then recovered to 55.07(17.99)Nm by 12-weeks (p = 0.028). By 12-weeks quadriceps strength was 70% and hamstrings 83% of the values achieved in the un-operated limb. Substantial improvement was seen in all other measures over time, with sequential positive change in Timed-up-and-go test (p = 0.015), 10 m walk test (p = 0.021), range of knee flexion (p = 0.016) and PROMs (p

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

Aims: The aims of this study were to assess mapping models to predict the three-level version of EuroQoL five-dimension utility index (EQ-5D-3L) from the Oxford Knee Score (OKS) and validate these before and after total knee arthroplasty (TKA). Methods: A retrospective cohort of 5,857 patients was used to create the prediction models, and a second cohort of 721 patients from a different centre was used to validate the models, all of whom underwent TKA. Patient characteristics, BMI, OKS, and EQ-5D-3L were collected preoperatively and one year postoperatively. Generalized linear regression was used to formulate the prediction models. Results: There were significant correlations between the OKS and EQ-5D-3L preoperatively (r = 0.68; p < 0.001) and postoperatively (r = 0.77; p < 0.001) and for the change in the scores (r = 0.61; p < 0.001). Three different models (preoperative, postoperative, and change) were created. There were no significant differences between the actual and predicted mean EQ-5D-3L utilities at any timepoint or for change in the scores (p > 0.090) in the validation cohort. There was a significant correlation between the actual and predicted EQ-5D-3L utilities preoperatively (r = 0.63; p < 0.001) and postoperatively (r = 0.77; p < 0.001) and for the change in the scores (r = 0.56; p < 0.001). Bland-Altman plots demonstrated that a lower utility was overestimated, and higher utility was underestimated. The individual predicted EQ-5D-3L that was within ± 0.05 and ± 0.010 (minimal clinically important difference (MCID)) of the actual EQ-5D-3L varied between 13% to 35% and 26% to 64%, respectively, according to timepoint assessed and change in the scores, but was not significantly different between the modelling and validation cohorts (p ≥ 0.148). Conclusion: The OKS can be used to estimate EQ-5D-3L. Predicted individual patient utility error beyond the MCID varied from one-third to two-thirds depending on timepoint assessed, but the mean for a cohort did not differ and could be employed for this purpose. Cite this article: Bone Jt Open 2022;3(7):573–581.

Abstract Background Gorham-Stout disease is a rare condition characterized by vascular proliferation and the massive destruction of bone tissue. With less than 400 cases in the literature of Gorham-Stout syndrome, we performed a unique study combining whole-genome sequencing and RNA-Seq to probe the genomic features and differentially expressed pathways of a presented case, revealing new possible drivers and biomarkers of the disease. Case presentation We present a case report of a white 45-year-old female patient with marked bone loss of the left humerus associated with vascular proliferation, diagnosed with Gorham-Stout disease. The analysis of whole-genome sequencing showed a dominance of large structural DNA rearrangements. Particularly, rearrangements in chromosomes seven, twelve, and twenty could contribute to the development of the disease, especially a gene fusion involving ATG101 that could affect macroautophagy. The study of RNA-sequencing data from the patient uncovered the PI3K/AKT/mTOR pathway as the most affected signaling cascade in the Gorham-Stout lesional tissue. Furthermore, M2 macrophage infiltration was detected using immunohistochemical staining and confirmed by deconvolution of the RNA-seq expression data. Conclusions The way that DNA and RNA aberrations lead to Gorham-Stout disease is poorly understood due to the limited number of studies focusing on this rare disease. Our study provides the first glimpse into this facet of the disease, exposing new possible therapeutic targets and facilitating the clinicopathological diagnosis of Gorham-Stout disease.

Abstract Background Epithelial-to-mesenchymal transition (EMT) is a process linked to metastasis and drug resistance with non-coding RNAs (ncRNAs) playing pivotal roles. We previously showed that miR-100 and miR-125b, embedded within the third intron of the ncRNA host gene MIR100HG, confer resistance to cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in colorectal cancer (CRC). However, whether the MIR100HG transcript itself has a role in cetuximab resistance or EMT is unknown. Methods The correlation between MIR100HG and EMT was analyzed by curating public CRC data repositories. The biological roles of MIR100HG in EMT, metastasis and cetuximab resistance in CRC were determined both in vitro and in vivo. The expression patterns of MIR100HG, hnRNPA2B1 and TCF7L2 in CRC specimens from patients who progressed on cetuximab and patients with metastatic disease were analyzed by RNAscope and immunohistochemical staining. Results The expression of MIR100HG was strongly correlated with EMT markers and acted as a positive regulator of EMT. MIR100HG sustained cetuximab resistance and facilitated invasion and metastasis in CRC cells both in vitro and in vivo. hnRNPA2B1 was identified as a binding partner of MIR100HG. Mechanistically, MIR100HG maintained mRNA stability of TCF7L2, a major transcriptional coactivator of the Wnt/β-catenin signaling, by interacting with hnRNPA2B1. hnRNPA2B1 recognized the N6-methyladenosine (m6A) site of TCF7L2 mRNA in the presence of MIR100HG. TCF7L2, in turn, activated MIR100HG transcription, forming a feed forward regulatory loop. The MIR100HG/hnRNPA2B1/TCF7L2 axis was augmented in specimens from CRC patients who either developed local or distant metastasis or had disease progression that was associated with cetuximab resistance. Conclusions MIR100HG and hnRNPA2B1 interact to control the transcriptional activity of Wnt signaling in CRC via regulation of TCF7L2 mRNA stability. Our findings identified MIR100HG as a potent EMT inducer in CRC that may contribute to cetuximab resistance and metastasis by activation of a MIR100HG/hnRNPA2B1/TCF7L2 feedback loop.

Abstract Walking is an important activity that supports the health-related quality of life, and for those who need assistance, robotic devices are available to help. Recent progress in wearable robots has identified the importance of customizing the assistance provided by the robot to the individual, resulting in robot adaptation to the human. However, current implementations minimize the role of human adaptation to the robot, for example, by the users modifying their movements based on the provided robot assistance. This study investigated the effect of visual feedback to guide the users in adapting their movements in response to wearable robot assistance. The visual feedback helped the users reduce their metabolic cost of walking without any changes in robot assistance in a given time. In a case with the initially metabolic expensive (IMExp) exoskeleton condition, both training methods helped reduce the metabolic cost of walking. The results suggest that visual feedback training is helpful to use the exoskeleton for various conditions. Without feedback, the training is helpful only for the IMExp exoskeleton condition. This result suggests visual feedback training can be useful to facilitate the use of non-personalized, generic assistance, where the assistance is not tuned for each user, in a relatively short time.

Abstract Background During vertebrate evolution, the heart has undergone remarkable changes that lead to morphophysiological differences in the fully formed heart of these species, such as chamber septation, heart rate frequency, blood pressure, and cardiac output volume. Despite these differences, the heart developmental process is guided by a core gene set conserved across vertebrates. Nonetheless, the regulatory mechanisms controlling the expression of genes involved in heart development and maintenance are largely uncharted. MicroRNAs (miRNAs) have been described as important regulatory elements in several biological processes, including heart biology. These small RNA molecules are broadly conserved in sequence and genomic context in metazoans. Mutations may occur in miRNAs and/or genes that contribute to the establishment of distinct repertoires of miRNA-target interactions, thereby favoring the differential control of gene expression and, consequently, the origin of novel phenotypes. In fact, several studies showed that miRNAs are integrated into genetic regulatory networks (GRNs) governing specific developmental programs and diseases. However, studies integrating miRNAs in vertebrate heart GRNs under an evolutionary perspective are still scarce. Results We comprehensively examined and compared the heart miRNome of 20 species representatives of the five major vertebrate groups. We found 54 miRNA families with conserved expression and a variable number of miRNA families with group-specific expression in fishes, amphibians, reptiles, birds, and mammals. We also detected that conserved miRNAs present higher expression levels and a higher number of targets, whereas the group-specific miRNAs present lower expression levels and few targets. Conclusions Both the conserved and group-specific miRNAs can be considered modulators orchestrating the core and peripheral genes of heart GRNs of vertebrates, which can be related to the morphophysiological differences and similarities existing in the heart of distinct vertebrate groups. We propose a hypothesis to explain evolutionary differences in the putative functional roles of miRNAs in the heart GRNs analyzed. Furthermore, we present new insights into the molecular mechanisms that could be helping modulate the diversity of morphophysiology in the heart organ of vertebrate species.

A potential treatment for retinal diseases is to induce an endogenous Müller glia (MG)-derived regenerative response to replace damaged neurons. In contrast to mammalian MG, zebrafish MG are capable of mediating spontaneous regeneration. We seek to define the mechanisms that enable retina regeneration in zebrafish in order to identify therapeutic targets to induce mammalian retina regeneration. We previously used pharmacological and genetic methods to inhibit gamma aminobutyric acid A (GABAA) receptors in undamaged zebrafish retinas and showed that such inhibition could induce initiation of retina regeneration, as measured by the dedifferentiation of MG and the appearance of MG-derived proliferating progenitor cells. Here, we show that inhibition of a pharmacologically distinct subset of GABAA receptors (GABAA-ρ) can also induce retina regeneration. Dual inhibition of both GABA receptor subtypes led to enhanced retina regeneration. Gene expression analyses indicate that inhibition of GABAA-ρ receptors induces a canonical retinal regenerative response. Our results support a model in which decreased levels of GABA, such as would occur after retinal cell death or damage, induce dedifferentiation of MG and the generation of proliferating progenitor cells during zebrafish retina regeneration. Animal experiments were approved by the Vanderbilt's Institutional Animal Care and Use Committee (Protocol M1800200) on January 29, 2019.

Aims: The primary aim of this study was to compare the hip-specific functional outcome of robotic assisted total hip arthroplasty (rTHA) with manual total hip arthroplasty (mTHA) in patients with osteoarthritis (OA). Secondary aims were to compare general health improvement, patient satisfaction, and radiological component position and restoration of leg length between rTHA and mTHA. Methods: A total of 40 patients undergoing rTHA were propensity score matched to 80 patients undergoing mTHA for OA. Patients were matched for age, sex, and preoperative function. The Oxford Hip Score (OHS), Forgotten Joint Score (FJS), and EuroQol five-dimension questionnaire (EQ-5D) were collected pre- and postoperatively (mean 10 months (SD 2.2) in rTHA group and 12 months (SD 0.3) in mTHA group). In addition, patient satisfaction was collected postoperatively. Component accuracy was assessed using Lewinnek and Callanan safe zones, and restoration of leg length were assessed radiologically. Results: There were no significant differences in the preoperative demographics (p ≥ 0.781) or function (p ≥ 0.383) between the groups. The postoperative OHS (difference 2.5, 95% confidence interval (CI) 0.1 to 4.8; p = 0.038) and FJS (difference 21.1, 95% CI 10.7 to 31.5; p < 0.001) were significantly greater in the rTHA group when compared with the mTHA group. However, only the FJS was clinically significantly greater. There was no difference in the postoperative EQ-5D (difference 0.017, 95% CI -0.042 to 0.077; p = 0.562) between the two groups. No patients were dissatisfied in the rTHA group whereas six were dissatisfied in the mTHA group, but this was not significant (p = 0.176). rTHA was associated with an overall greater rate of component positioning in a safe zone (p ≤ 0.003) and restoration of leg length (p < 0.001). Conclusion: Patients undergoing rTHA had a greater hip-specific functional outcome when compared to mTHA, which may be related to improved component positioning and restoration of leg length. However, there was no difference in their postoperative generic health or rate of satisfaction.

Abstract Background Clinical practice typically emphasizes active involvement during therapy. However, traditional approaches can offer only general guidance on the form of involvement that would be most helpful to recovery. Beyond assisting movement, robots allow comprehensive methods for measuring practice behaviors, including the energetic input of the learner. Using data from our previous study of robot-assisted therapy, we examined how separate components of mechanical work contribute to predicting training outcomes. Methods Stroke survivors (n = 11) completed six sessions in two-weeks of upper extremity motor exploration (self-directed movement practice) training with customized forces, while a control group (n = 11) trained without assistance. We employed multiple regression analysis to predict patient outcomes with computed mechanical work as independent variables, including separate features for elbow versus shoulder joints, positive (concentric) and negative (eccentric), flexion and extension. Results Our analysis showed that increases in total mechanical work during therapy were positively correlated with our final outcome metric, velocity range. Further analysis revealed that greater amounts of negative work at the shoulder and positive work at the elbow as the most important predictors of recovery (using cross-validated regression, R2 = 52%). However, the work features were likely mutually correlated, suggesting a prediction model that first removed shared variance (using PCA, R2 = 65–85%). Conclusions These results support robotic training for stroke survivors that increases energetic activity in eccentric shoulder and concentric elbow actions. Trial registration ClinicalTrials.gov , Identifier: NCT02570256 . Registered 7 October 2015 – Retrospectively registered,

Extracellular vesicles (EVs) are capable of transferring cargo from donor to recipient cells, but precisely how cargo content is regulated for export is mostly unknown. For miRNA cargo, we previously showed that when compared to isogenic colorectal cancer (CRC) cells expressing wild-type KRAS, a distinct subset of miRNAs are differentially enriched in EVs from KRAS mutant active CRC cells, with miR-100 being one of the most enriched. The mechanisms that could explain how miR-100 and other miRNAs are differentially exported into EVs have not been fully elucidated. Here, we tested the effect of N6-methyladenosine (m6A) modification on miRNA export into EVs by depletion of METTL3 and ALKBH5, a writer and eraser of m6A modification, respectively. While the effects of ALKBH5 knockdown were quite modest, decreased levels of METTL3 led to reduced cellular and extracellular levels of a subset of miRNAs that contain consensus sequences for m6A modification. Functional testing of EVs prepared from cells expressing shRNAs against METTL3 showed that they were less capable of conferring colony growth in 3D to wild-type KRAS cells and were also largely incapable of conferring the spread of cetuximab resistance. Our data support a role for METTL3 modification on cellular miRNA levels and export of specific miRNAs.

During motor learning, people often practice reaching in variety of movement directions in a randomized sequence. Such training has been shown to enhance retention and transfer capability of the acquired skill compared to the blocked repetition of the same movement direction. The learning system must accommodate such randomized order either by having a memory for each movement direction, or by being able to generalize what was learned in one movement direction to the controls of nearby directions. While our preliminary study used a comprehensive dataset from visuomotor learning experiments and evaluated the first-order model candidates that considered the memory of error and generalization across movement directions, here we expanded our list of candidate models that considered the higher-order effects and error-dependent learning rates. We also employed cross-validation to select the leading models. We found that the first-order model with a constant learning rate was the best at predicting learning curves. This model revealed an interaction between the learning and forgetting processes using the direction-specific memory of error. As expected, learning effects were observed at the practiced movement direction on a given trial. Forgetting effects (error increasing) were observed at the unpracticed movement directions with learning effects from generalization from the practiced movement direction. Our study provides insights that guide optimal training using the machine-learning algorithms in areas such as sports coaching, neurorehabilitation, and human-machine interactions.

The use of model systems that are capable of robust, spontaneous retina regeneration has allowed for the identification of genetic pathways and components that are required for retina regeneration. Complemented by mouse models in which retina regeneration can be induced after forced expression of key factors, altered chromatin accessibility, or inhibition of kinase/signaling cascades, a clearer picture of the key regulatory events that control retina regeneration is emerging. In all cases, Müller glia (MG) serve as an adult retinal stem cell that must be reprogrammed to allow for regeneration, with the end goal being to understand why regenerative pathways are blocked in mammals, but spontaneous in other vertebrates such as zebrafish. miRNAs have emerged as key gene regulatory molecules that control both development and regeneration in vertebrates. Here, we focus on a small subset of miRNAs that control MG reprogramming during retina regeneration and have the potential to serve as therapeutic targets for treatment of visual disorders and damage.