Restoring vision using optogenetics without being blind to the risks
Ontology highlight
ABSTRACT:
SUBMITTER: Harris A
PROVIDER: S-EPMC8558540 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Degenerative retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) affect millions of people around the world and lead to irreversible vision loss if left untreated. A number of therapeutic strategies have been developed over the years to treat these diseases or restore vision to already blind patients. In this Review, we describe the development and translational application of light-sensitive chemical photoswitches to restore visual function to the blind retina and compare the translational potential of photoswitches with other vision-restoring therapies. This therapeutic strategy is enabled by an efficient fusion of chemical synthesis, chemical biology, and molecular biology and is broadly applicable to other biological systems. We hope this Review will be of interest to chemists as well as neuroscientists and clinicians.
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Project description:Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery of ChRmine, we demonstrate behavioral modulation without surgery, enabling implant-free deep brain optogenetics.
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Project description:PURPOSE:To report the initial efficacy results of the Retina Implant Alpha AMS (Retina Implant AG, Reutlingen, Germany) for partial restoration of vision in end-stage retinitis pigmentosa (RP). DESIGN:Prospective, single-arm, investigator-sponsored interventional clinical trial. Within-participant control comprising residual vision with the retinal implant switched ON versus OFF in the implanted eye. PARTICIPANTS:The Retina Implant Alpha AMS was implanted into the worse-seeing eye of 6 participants with end-stage RP and no useful perception of light vision. Eligibility criteria included previous normal vision for ?12 years and no significant ocular or systemic comorbidity. METHODS:Vision assessments were scheduled at 1, 2, 3, 6, 9, and 12 months postimplantation. They comprised tabletop object recognition tasks, a self-assessment mobility questionnaire, and screen-based tests including Basic Light and Motion (BaLM), grating acuity, and greyscale contrast discrimination. A full-field stimulus test (FST) was also performed. MAIN OUTCOME MEASURES:Improvement in activities of daily living, recognition tasks, and assessments of light perception with the implant ON compared with OFF. RESULTS:All 6 participants underwent successful implantation. Light perception and temporal resolution with the implant ON were achieved in all participants. Light localization was achieved with the implant ON in all but 1 participant (P4) in whom the chip was not functioning optimally because of a combination of iatrogenic intraoperative implant damage and incorrect implantation. Implant ON correct grating detections (which were at chance level with implant OFF) were recorded in the other 5 participants, ranging from 0.1 to 3.33 cycles/degree on 1 occasion. The ability to locate high-contrast tabletop objects not seen with the implant OFF was partially restored with the implant ON in all but 1 participant (P4). There were 2 incidents of conjunctival erosion and 1 inferotemporal macula-on retinal detachment, which were successfully repaired, and 2 incidents of inadvertent damage to the implant during surgery (P3 and P4). CONCLUSIONS:The Alpha AMS subretinal implant improved visual performance in 5 of 6 participants and has exhibited ongoing function for up to 24 months. Although implantation surgery remains challenging, new developments such as OCT microscope guidance added refinements to the surgical technique.
| S-EPMC5818267 | biostudies-literature
Project description:Retinal degenerative diseases can have many possible causes and are currently difficult to treat. As an alternative to therapies that require genetic manipulation or the implantation of electronic devices, photopharmacology has emerged as a viable approach to restore visual responses. Here, we present a new photopharmacological strategy that relies on a photoswitchable excitatory amino acid, ATA. This freely diffusible molecule selectively activates AMPA receptors in a light-dependent fashion. It primarily acts on amacrine and retinal ganglion cells, although a minor effect on bipolar cells has been observed. As such, it complements previous pharmacological approaches based on photochromic channel blockers and increases the potential of photopharmacology in vision restoration.
| S-EPMC4722500 | biostudies-literature
Project description:Purpose of reviewWe summarize recent advances in strategies that aim to restore optic nerve function and vision in glaucoma through protective, reparative, and regenerative avenues.Recent findingsNeuroprotection relies on identification of early retinal ganglion cell dysfunction, which could prove challenging in the clinic. Cell replacement therapies show promise in restoring lost vision, but some hurdles remain in restoring visual circuitry in the retina and central connections in the brain.SummaryIdentification and manipulation of intrinsic and extrinsic cellular mechanisms that promote axon regeneration in both resident and transplanted RGCs will drive future advances in vision restoration. Understanding the roles of multiple cell types in the retina that act in concert to promote RGC survival will aid efforts to promote neuronal health and restoration. Effective RGC transplantation, fine tuning axon guidance and growth, and synaptogenesis of transplanted and resident RGCs are still areas that require more research.
| S-EPMC7686214 | biostudies-literature
Project description:Visual information is extremely important to generate internal spatial representations. In the auditory modality, the absence of visual cues during early infancy does not preclude the development of some spatial strategies. However, specific spatial abilities might result impaired. In the current study, we investigated the effect of early visual deprivation on the ability to localize static and moving auditory stimuli by comparing sighted and early blind individuals' performance in different spatial tasks. We also examined perceptual stability in the two groups of participants by matching localization accuracy in a static and a dynamic head condition that involved rotational head movements. Sighted participants accurately localized static and moving sounds. Their localization ability remained unchanged after rotational movements of the head. Conversely, blind participants showed a leftward bias during the localization of static sounds and a little bias for moving sounds. Moreover, head movements induced a significant bias in the direction of head motion during the localization of moving sounds. These results suggest that internal spatial representations might be body-centered in blind individuals and that in sighted people the availability of visual cues during early infancy may affect sensory-motor interactions.
| S-EPMC5421809 | biostudies-literature
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
Project description:Recently developed optogenetic methods promise to revolutionize cell biology by allowing signaling perturbations to be controlled in space and time with light. However, a quantitative analysis of the relationship between a custom-defined illumination pattern and the resulting signaling perturbation is lacking. Here, we characterize the biophysical processes governing the localized recruitment of the Cryptochrome CRY2 to its membrane-anchored CIBN partner. We develop a quantitative framework and present simple procedures that enable predictive manipulation of protein distributions on the plasma membrane with a spatial resolution of 5 ?m. We show that protein gradients of desired levels can be established in a few tens of seconds and then steadily maintained. These protein gradients can be entirely relocalized in a few minutes. We apply our approach to the control of the Cdc42 Rho GTPase activity. By inducing strong localized signaling perturbation, we are able to monitor the initiation of cell polarity and migration with a remarkable reproducibility despite cell-to-cell variability.
| S-EPMC4643200 | biostudies-literature
Project description:Rotating spiral waves in the heart are associated with life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation. These arrhythmias are treated by a process called defibrillation, which forces electrical resynchronization of the heart tissue by delivering a single global high-voltage shock directly to the heart. This method leads to immediate termination of spiral waves. However, this may not be the only mechanism underlying successful defibrillation, as certain scenarios have also been reported, where the arrhythmia terminated slowly, over a finite period of time. Here, we investigate the slow termination dynamics of an arrhythmia in optogenetically modified murine cardiac tissue both in silico and ex vivo during global illumination at low light intensities. Optical imaging of an intact mouse heart during a ventricular arrhythmia shows slow termination of the arrhythmia, which is due to action potential prolongation observed during the last rotation of the wave. Our numerical studies show that when the core of a spiral is illuminated, it begins to expand, pushing the spiral arm towards the inexcitable boundary of the domain, leading to termination of the spiral wave. We believe that these fundamental findings lead to a better understanding of arrhythmia dynamics during slow termination, which in turn has implications for the improvement and development of new cardiac defibrillation techniques.
| S-EPMC10729946 | biostudies-literature
Project description:BackgroundThe purpose of the study is to investigate the changes of macular perfusion by OCT-angiography (OCT-A) after uncomplicated phacoemulsification.MethodsOCT-A was performed before cataract surgery, 1 week, 1 month, and 3 months after surgery recording superficial vascular complex (SVC), nerve fiber layer vascular plexus (NFLVP), superficial vascular plexus (SVP), deep vascular complex (DVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), as well as large choroidal blood vessels and choriocapillaris (CC). Explant area (EA), vessels area (VA), vessels percentage area (VPA), total number of junctions (TNJ), junctions density (JD), total vessels length (TVL), average vessels length (AVL), total number of end points (TNEP), and mean lacunarity (ML) throughout all layers were analysed.ResultsSignificant changes of vascular parameters in 55 eyes of 55 patients mostly reached plateau one week after surgery and remained stable up to 3 m after surgery, occurring in all retinal layers but not in choroid and CC. The greatest increase in VPA (22.79%), TVL (16.71%), AVL (166.71%) and JD (29.49%) was in SVC. On the contrary, the greatest change of ML (- 53.41%) appeared in DVC.ConclusionsThis is the first OCT-A study demonstrating perfusion alterations in macula after phacoemulsification due to functional hyperaemia. We presume the effect is evoked by increased light intensity stimulation of retina after cataract removal. Accordingly, phacoemulsification in elderly population could have advantageous feature in addition to restoring visual acuity.
| S-EPMC7863317 | biostudies-literature