Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regenerating Eye Tissues to Preserve and Restore Vision.

ABSTRACT: Ocular regenerative therapies are on track to revolutionize treatment of numerous blinding disorders, including corneal disease, cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. A variety of transplantable products, delivered as cell suspensions or as preformed 3D structures combining cells and natural or artificial substrates, are in the pipeline. Here we review the status of clinical and preclinical studies for stem cell-based repair, covering key eye tissues from front to back, from cornea to retina, and including bioengineering approaches that advance cell product manufacturing. While recognizing the challenges, we look forward to a deep portfolio of sight-restoring, stem cell-based medicine. VIDEO ABSTRACT.

SUBMITTER: Stern JH

PROVIDER: S-EPMC6492284 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Regenerating Eye Tissues to Preserve and Restore Vision.

Stern Jeffrey H JH Tian Yangzi Y Funderburgh James J Pellegrini Graziella G Zhang Kang K Goldberg Jeffrey L JL Ali Robin R RR Young Michael M Xie Yubing Y Temple Sally S

Cell stem cell 20180601 6

Ocular regenerative therapies are on track to revolutionize treatment of numerous blinding disorders, including corneal disease, cataract, glaucoma, retinitis pigmentosa, and age-related macular degeneration. A variety of transplantable products, delivered as cell suspensions or as preformed 3D structures combining cells and natural or artificial substrates, are in the pipeline. Here we review the status of clinical and preclinical studies for stem cell-based repair, covering key eye tissues fro ...[more]

PMID: 29859174

Similar Datasets

Reprogramming to recover youthful epigenetic information and restore vision

Project description:Epigenetic reprogramming via a combination of three Yamanaka factors, Oct4, Sox2, and Klf4 (OSK), provides an effective way to promote axon regeneration in chemical- or injury-damaged neurons and improve neuronal function in aged mice. DNA methylation landscape is remodeled during this reprogramming process. This study was designed to examine DNA methylation age in differentiated human neurons post axonal damage with or without OSK expression. Differentiated SH-SY5Y neurons were transduced with AAV.DJ vectors to induce OSK expression for five days, followed by 24-hr treatment with 100nM vincristine (VCS) to induce neurite degeneration. Neurons were harvested at either day 1 or day 9 after VCS treatment. The Illumina Infinium DNA methylation EPIC array was used to obtain DNA methylation profiles. The skin & blood clock from Horvath 2018 (PMID: 30048243 PMCID: PMC6075434) was used for DNA methylation age analysis.

2020-09-26 | GSE147436 | GEO

Nanowire arrays restore vision in blind mice.

Project description:The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100?µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.

| S-EPMC5840349 | biostudies-literature

Reprogramming to recover youthful epigenetic information and restore vision.

Project description:Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1-3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.

| S-EPMC7752134 | biostudies-literature

Retinal prosthetic strategy with the capacity to restore normal vision.

Project description:Retinal prosthetics offer hope for patients with retinal degenerative diseases. There are 20-25 million people worldwide who are blind or facing blindness due to these diseases, and they have few treatment options. Drug therapies are able to help a small fraction of the population, but for the vast majority, their best hope is through prosthetic devices [reviewed in Chader et al. (2009) Prog Brain Res 175:317-332]. Current prosthetics, however, are still very limited in the vision that they provide: for example, they allow for perception of spots of light and high-contrast edges, but not natural images. Efforts to improve prosthetic capabilities have focused largely on increasing the resolution of the device's stimulators (either electrodes or optogenetic transducers). Here, we show that a second factor is also critical: driving the stimulators with the retina's neural code. Using the mouse as a model system, we generated a prosthetic system that incorporates the code. This dramatically increased the system's capabilities--well beyond what can be achieved just by increasing resolution. Furthermore, the results show, using 9,800 optogenetically stimulated ganglion cell responses, that the combined effect of using the code and high-resolution stimulation is able to bring prosthetic capabilities into the realm of normal image representation.

| S-EPMC3443127 | biostudies-literature

Predictive eye movements in natural vision.

Project description:In the natural world, the brain must handle inherent delays in visual processing. This is a problem particularly during dynamic tasks. A possible solution to visuo-motor delays is prediction of a future state of the environment based on the current state and properties of the environment learned from experience. Prediction is well known to occur in both saccades and pursuit movements and is likely to depend on some kind of internal visual model as the basis for this prediction. However, most evidence comes from controlled laboratory studies using simple paradigms. In this study, we examine eye movements made in the context of demanding natural behavior, while playing squash. We show that prediction is a pervasive component of gaze behavior in this context. We show in addition that these predictive movements are extraordinarily precise and operate continuously in time across multiple trajectories and multiple movements. This suggests that prediction is based on complex dynamic visual models of the way that balls move, accumulated over extensive experience. Since eye, head, arm, and body movements all co-occur, it seems likely that a common internal model of predicted visual state is shared by different effectors to allow flexible coordination patterns. It is generally agreed that internal models are responsible for predicting future sensory state for control of body movements. The present work suggests that model-based prediction is likely to be a pervasive component in natural gaze control as well.

| S-EPMC3328199 | biostudies-literature

A sensory memory to preserve visual representations across eye movements.

Project description:Saccadic eye movements (saccades) disrupt the continuous flow of visual information, yet our perception of the visual world remains uninterrupted. Here we assess the representation of the visual scene across saccades from single-trial spike trains of extrastriate visual areas, using a combined electrophysiology and statistical modeling approach. Using a model-based decoder we generate a high temporal resolution readout of visual information, and identify the specific changes in neurons' spatiotemporal sensitivity that underly an integrated perisaccadic representation of visual space. Our results show that by maintaining a memory of the visual scene, extrastriate neurons produce an uninterrupted representation of the visual world. Extrastriate neurons exhibit a late response enhancement close to the time of saccade onset, which preserves the latest pre-saccadic information until the post-saccadic flow of retinal information resumes. These results show how our brain exploits available information to maintain a representation of the scene while visual inputs are disrupted.

| S-EPMC8575989 | biostudies-literature

Targeting Caspase-12 to Preserve Vision in Mice With Inherited Retinal Degeneration.

Project description:PurposeThe unfolded protein response is known to contribute to the inherited retinal pathology observed in T17M rhodopsin (T17M) mice. Recently it has been demonstrated that the endoplasmic reticulum stress-associated caspase-12 is activated during progression of retinal degeneration in different animal models. Therefore, we wanted to explore the role of caspase-12 in the mechanism of retinopathy in T17M mice and determine if inhibiting apoptosis in this way is a viable approach for halting retinal degeneration.MethodsOne, two-, and three-month-old C57BL6/J, caspase-12-/-, T17M, and T17M caspase-12-/- mice were analyzed by scotopic ERG, spectral-domain optical coherence tomography (SD-OCT), histology, quantitative (q)RT-PCR, and Western blot of retinal RNA and protein extracts. Calpain and caspase-3/7 activity assays were measured in postnatal (P) day 30 retinal extracts.ResultsCaspase-12 ablation significantly prevented a decline in the a- and b-wave ERG amplitudes in T17M mice during three months, increasing the amplitudes from 232% to 212% and from 160% to 138%, respectively, as compared to T17M retinas. The SD-OCT results and photoreceptor row counts demonstrated preservation of retinal structural integrity and postponed photoreceptor cell death. The delay in photoreceptor cell death was due to significant decreases in the activity of caspase-3/7 and calpain, which correlated with an increase in calpastatin expression.ConclusionsWe validated caspase-12 as a therapeutic target, ablation of which significantly protects T17M photoreceptors from deterioration. Although the inhibition of apoptotic activity alone was not sufficient to rescue T17M photoreceptors, in combination with other nonapoptotic targets, caspase-12 could be used to treat inherited retinopathy.

| S-EPMC4516015 | biostudies-literature

Subanesthetic Ketamine Reactivates Adult Cortical Plasticity to Restore Vision from Amblyopia.

Project description:Subanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine's effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces downregulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus, ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.

| S-EPMC7925140 | biostudies-literature

Potential therapeutic strategies for photoreceptor degeneration: the path to restore vision.

Project description:Photoreceptors (PRs), as the most abundant and light-sensing cells of the neuroretina, are responsible for converting light into electrical signals that can be interpreted by the brain. PR degeneration, including morphological and functional impairment of these cells, causes significant diminution of the retina's ability to detect light, with consequent loss of vision. Recent findings in ocular regenerative medicine have opened promising avenues to apply neuroprotective therapy, gene therapy, cell replacement therapy, and visual prostheses to the challenge of restoring vision. However, successful visual restoration in the clinical setting requires application of these therapeutic approaches at the appropriate stage of the retinal degeneration. In this review, firstly, we discuss the mechanisms of PR degeneration by focusing on the molecular mechanisms underlying cell death. Subsequently, innovations, recent developments, and promising treatments based on the stage of disorder progression are further explored. Then, the challenges to be addressed before implementation of these therapies in clinical practice are considered. Finally, potential solutions to overcome the current limitations of this growing research area are suggested. Overall, the majority of current treatment modalities are still at an early stage of development and require extensive additional studies, both pre-clinical and clinical, before full restoration of visual function in PR degeneration diseases can be realized.

| S-EPMC9727916 | biostudies-literature

Plasmonic ommatidia for lensless compound-eye vision.

Project description:The vision system of arthropods such as insects and crustaceans is based on the compound-eye architecture, consisting of a dense array of individual imaging elements (ommatidia) pointing along different directions. This arrangement is particularly attractive for imaging applications requiring extreme size miniaturization, wide-angle fields of view, and high sensitivity to motion. However, the implementation of cameras directly mimicking the eyes of common arthropods is complicated by their curved geometry. Here, we describe a lensless planar architecture, where each pixel of a standard image-sensor array is coated with an ensemble of metallic plasmonic nanostructures that only transmits light incident along a small geometrically-tunable distribution of angles. A set of near-infrared devices providing directional photodetection peaked at different angles is designed, fabricated, and tested. Computational imaging techniques are then employed to demonstrate the ability of these devices to reconstruct high-quality images of relatively complex objects.

| S-EPMC7118074 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data