Volume electron microscopy

Nature Reviews Methods Primers, Journal Year: 2022, Volume and Issue: 2(1)

Published: July 7, 2022

Language: Английский

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Light-induced charge generation in polymeric nanoparticles restores vision in advanced-stage retinitis pigmentosa rats

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 27, 2022

Abstract Retinal dystrophies such as Retinitis pigmentosa are among the most prevalent causes of inherited legal blindness, for which treatments in demand. prostheses have been developed to stimulate inner retinal network that, initially spared by degeneration, deteriorates late stages disease. We recently reported that conjugated polymer nanoparticles persistently rescue visual activities after a single subretinal injection Royal College Surgeons rat model . Here we demonstrate can reinstate physiological signals at cortical level and visually driven when microinjected 10-months-old rats bearing fully light-insensitive retinas. The extent restoration positively correlates with nanoparticle density hybrid contacts second-order neurons. results establish functional role organic photovoltaic restoring degenerate retinas intense retina rewiring, stage disease patients subjected prosthetic interventions.

Language: Английский

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Optogenetics for visual restoration: From proof of principle to translational challenges

Progress in Retinal and Eye Research, Journal Year: 2022, Volume and Issue: 91, P. 101089 - 101089

Published: June 10, 2022

Degenerative retinal disorders are a diverse family of diseases commonly leading to irreversible photoreceptor death, while leaving the inner retina relatively intact. Over recent years, innovative gene replacement therapies aiming halt progression certain inherited have made their way into clinics. By rendering surviving neurons light sensitive optogenetic therapy now offers feasible treatment option that can restore lost vision, even in late disease stages and widely independent underlying cause degeneration. Since proof-of-concept almost fifteen years ago, this field has rapidly evolved detailed first report on treated patient recently been published. In article, we provide review approaches for vision restoration. We discuss currently available tools relative advantages disadvantages. Possible cellular targets will be discussed address question how remodelling may affect choice target what extent it limit outcomes Finally, analyse evidence against tool mediated toxicity challenges associated with clinical translation promising therapeutic concept.

Language: Английский

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Molecular basis of retinal remodeling in a zebrafish model of retinitis pigmentosa

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(12)

Published: Nov. 18, 2023

A hallmark of inherited retinal degenerative diseases such as retinitis pigmentosa (RP) is progressive structural and functional remodeling the remaining cells photoreceptors degenerate. Extensive retina stands a barrier for successful implementation strategies to restore vision. To understand molecular basis remodeling, we performed analyses single-cell transcriptome data from adult zebrafish wild type AB strain (WT) P23H mutant rhodopsin transgenic model RP with continuous degeneration regeneration. Retinas both female male fish were pooled generate each library, combining sexes. We provide benchmark atlas cell transcriptomes in insight into how affected model. Oxidative stress found throughout retina, increases reliance on oxidative metabolism glycolysis rods well cones, bipolar cells, ganglion cells. There also transcriptional evidence widespread synaptic enhancement glutamatergic transmission inner retina. Notably, changes circadian rhythm regulation are detected pigmented epithelium. identify transcriptomic signatures progenitor newly formed essential regenerative process. This comprehensive analysis provides road map remodels context chronic ongoing

Language: Английский

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Nanoparticle-based optical interfaces for retinal neuromodulation: a review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 20, 2024

Degeneration of photoreceptors in the retina is a leading cause blindness, but commonly leaves retinal ganglion cells (RGCs) and/or bipolar extant. Consequently, these are an attractive target for invasive electrical implants colloquially known as “bionic eyes.” However, after more than two decades concerted effort, interfaces based on conventional stimulation approaches have delivered limited efficacy, primarily due to current spread tissue, which precludes high-acuity vision. The ideal prosthetic solution would be less invasive, provide single-cell resolution and ability differentiate between different cell types. Nanoparticle-mediated can address some requirements, with particular attention being directed at light-sensitive nanoparticles that accessed via intrinsic optics eye. Here we survey available nanoparticle-based optical transduction mechanisms exploited neuromodulation. We review rapid progress field, together outstanding challenges must addressed translate techniques clinical practice. In particular, successful translation will likely require efficient delivery stable precisely defined locations tissues. Therefore, also emphasize literature relating pharmacokinetics While considerable remain overcome, date shows great potential revolutionize field visual prostheses.

Language: Английский

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Fast imaging of millimeter-scale areas with beam deflection transmission electron microscopy

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 10, 2024

Serial section transmission electron microscopy (TEM) has proven to be one of the leading methods for millimeter-scale 3D imaging brain tissues at nanoscale resolution. It is important further improve efficiency acquire larger and more volumes. We report here a threefold increase in speed TEM by using beam deflecting mechanism enable highly efficient acquisition multiple image tiles (nine) each motion mechanical stage. For areas, duty cycle doubles than 30%, yielding net average rate 0.3 gigapixels per second. If fully utilized, an array four deflection TEMs should capable dataset cubic millimeter scale five weeks.

Language: Английский

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Distinctive synaptic structural motifs link excitatory retinal interneurons to diverse postsynaptic partner types

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 112006 - 112006

Published: Jan. 1, 2023

Neurons make converging and diverging synaptic connections with distinct partner types. Whether synapses involving separate partners demonstrate similar or structural motifs is not yet well understood. We thus used serial electron microscopy in mouse retina to map output of cone bipolar cells (CBCs) compare their arrangements across types postsynaptic partners. Three presynaptic configurations emerge—single-ribbon, ribbonless, multiribbon synapses. Each CBC type exploits these a unique combination, feature also found among rabbit ON CBCs. Though most are dyads, monads triads seen. Altogether, CBCs exhibit at least six motifs, each uses stereotypic pattern. Moreover, between particular appear biased toward certain motifs. Our observations reveal strategies that diversify the within types, potentially shaping functions retinal microcircuits.

Language: Английский

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Optogenetic therapy for retinal degenerative diseases: A review

European Journal of Ophthalmology, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Optogenetics, a cutting-edge tool in novel gene manipulation and drug discovery, holds significant therapeutic potential for variety of neurological disorders, including retinal diseases. Retinal diseases such as age-related macular degeneration (AMD) retinitis pigmentosa (RP), significantly impair quality life cause severe visual impairment due to limited treatment options general lack awareness. The increasing incidence these degenerative conditions underscores the need innovative solutions, optogenetics. Optogenetic therapy introduces genes coding light-sensitive proteins, which are controlled by light signals make neurons photosensitive. This precise targeting approach does not require specific intervention can bypass dysfunctional photoreceptors, offering option various dystrophic eye Successful outcomes patients with late-stage genetic numerous clinical trials suggest that optogenetics could be an effective humans. review provides overview current landscape optogenetic therapy, discusses its challenges, summarizes findings ongoing neural restoration.

Language: Английский

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The Pupillary Light Reflex as a Biomarker of Concussion

Life, Journal Year: 2021, Volume and Issue: 11(10), P. 1104 - 1104

Published: Oct. 18, 2021

The size of our pupils changes continuously in response to variations ambient light levels, a process known as the pupillary reflex (PLR). PLR is not simple its function modulated by cognitive brain and any long-term secondary injury should cause change parameters PLR. We performed retrospective clinical review patients using BrightLamp Reflex iPhone app. variables latency, maximum pupil diameter (MaxPD), minimum (MinPD), constriction velocity (MCV), 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered concussion those that not. There also metrics over life span genders without symptoms. are only history but gender whether or person has symptoms head injury. A concussive persist span, representing biomarkers might be used diagnosis, treatment, decision making.

Language: Английский

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Homeostatic plasticity in the retina

Progress in Retinal and Eye Research, Journal Year: 2022, Volume and Issue: 94, P. 101131 - 101131

Published: Oct. 13, 2022

Language: Английский

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