Nanoparticle-based optical interfaces for retinal neuromodulation: a review DOI Creative Commons
Paul R. Stoddart, James M. Begeng, Wei Tong

et al.

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

Retinitis Pigmentosa: Progress in Molecular Pathology and Biotherapeutical Strategies DOI Open Access
Wanqin Liu, Shanshan Liu, Ping Li

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(9), P. 4883 - 4883

Published: April 28, 2022

Retinitis pigmentosa (RP) is genetically heterogeneous retinopathy caused by photoreceptor cell death and retinal pigment epithelial atrophy that eventually results in blindness bilateral eyes. Various types pathological phenotypic changes have been disclosed RP demand in-depth research of its pathogenic mechanism may account for inter-patient responses to mainstream drug treatment. As the primary method studying genetic characteristics RP, molecular biology has widely used disease diagnosis clinical trials. Current technology iterations, such as gene therapy, stem optogenetics, are advancing towards precise applications. Specifically, technologies, effective delivery vectors, CRISPR/Cas9 technology, iPSC-based transplantation, hasten pace personalized precision medicine RP. The combination conventional therapy state-of-the-art medication promising revolutionizing treatment strategies. This article provides an overview latest on pathogenesis, diagnosis, retinitis pigmentosa, aiming a convenient reference what achieved so far.

Language: Английский

Citations

94
Bioengineering strategies for restoring vision DOI
Jasmina Cehajic‐Kapetanovic, Mandeep S. Singh, Eberhart Zrenner

et al.

Nature Biomedical Engineering, Journal Year: 2022, Volume and Issue: 7(4), P. 387 - 404

Published: Jan. 31, 2022

Language: Английский

Citations

57
Light-induced charge generation in polymeric nanoparticles restores vision in advanced-stage retinitis pigmentosa rats DOI Creative Commons
Simona Francia, Dmytro Shmal, Stefano Di Marco

et al.

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

Citations

48
Adeno-Associated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We? DOI Creative Commons
Divya Ail, Hugo Malki, Emilia A. Zin

et al.

The Application of Clinical Genetics, Journal Year: 2023, Volume and Issue: Volume 16, P. 111 - 130

Published: May 1, 2023

Abstract: Owing to their small size and safety profiles, adeno-associated viruses (AAVs) have become the vector of choice for gene therapy applications in retina. In addition naturally occurring AAVs, several engineered variants with enhanced properties are being developed experimental therapeutic applications. Nonetheless, there still some challenges impeding successful application AAVs a broader range retinal therapies. The AAV particles ensures efficient tissue transduction but also limits packaging capacity few kilobases. Further, AAV's ability cross barriers is an obstacle pan-retinal outer retina tolerable doses. Lastly, despite overall safety, been recent reports immune responses eye. Hence, evaluation prediction has come be considered integral part future clinical success. This review focuses on use trials diseases, discusses developments novel strategies overcome AAVs. Keywords: therapy, virus, AAV, trials, capsid variants,

Language: Английский

Citations

31
The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease DOI Creative Commons
Sarah X. Zhang, Josh J. Wang, Christopher R. Starr

et al.

Progress in Retinal and Eye Research, Journal Year: 2023, Volume and Issue: 98, P. 101231 - 101231

Published: Dec. 12, 2023

Language: Английский

Citations

28
Gene-agnostic therapeutic approaches for inherited retinal degenerations DOI Creative Commons

Molly C. John,

Joel Quinn, Monica L. Hu

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 9, 2023

Inherited retinal diseases (IRDs) are associated with mutations in over 250 genes and represent a major cause of irreversible blindness worldwide. While gene augmentation or editing therapies could address the underlying genetic small subset patients, their utility remains limited by great heterogeneity IRDs costs developing individualised therapies. Gene-agnostic therapeutic approaches target common pathogenic pathways that drive degeneration provide functional rescue vision independent cause, thus offering potential clinical benefits to all IRD patients. Here, we review key gene-agnostic approaches, including cell reprogramming replacement, neurotrophic support, immune modulation optogenetics. The relative limitations these strategies timing interventions discussed.

Language: Английский

Citations

25
Müller Glial Cells in the Macula: Their Activation and Cell-Cell Interactions in Age-Related Macular Degeneration DOI Creative Commons

Soumya Navneet,

Kyrie Wilson,

Bärbel Rohrer

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(2), P. 42 - 42

Published: Feb. 28, 2024

Müller glia, the main glial cell of retina, are critical for neuronal and vascular homeostasis in retina. During age-related macular degeneration (AMD) pathogenesis, activation, remodeling, migrations reported areas retinal pigment epithelial (RPE) degeneration, photoreceptor loss, choroidal neovascularization (CNV) lesions. Despite this evidence indicating activation localized to regions AMD it is unclear whether these responses contribute pathology or occur merely as a bystander effect. In review, we summarize how glia affected retinas share prospect on stress might directly pathogenesis AMD. The goal review highlight need future studies investigating cell's role This may lead better understanding pathology, including conversion from dry wet AMD, which has no effective therapy currently shed light drug intolerance resistance current treatments.

Language: Английский

Citations

15
ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY DOI Creative Commons
Jessica Rodgers, Steven Hughes, Aghileh S. Ebrahimi

et al.

Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 1264 - 1281

Published: Jan. 18, 2025

Language: Английский

Citations

1
Circadian clock disruption promotes retinal photoreceptor degeneration DOI Creative Commons
Shumet T. Gegnaw, Cristina Sandu, Amandine Béry

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(7)

Published: April 2, 2025

Daily rhythms are a central hallmark of vision, in particular by adapting retinal physiology and light response to the day-night cycle. These cyclic processes regulated circadian clocks, molecular machineries regulating gene expression across 24-h Although hundreds genes associated with genetic disorders have been identified, no direct link has established clock. Hence, we investigated hypothesis that poorly functioning clock aggravates photoreceptor disease. We performed this study P23H rhodopsin-mutated mouse model (P23H Rho) mimics one major cause human autosomal dominant retinitis pigmentosa. also used rod-specific knockout (rod-Bmal1KO) Bmal1, key component. More specifically, either heterozygous Rho mice or rod-Bmal1KO alone, as well double mutants these strains control mice. showed structural (histology, immunohistochemistry) functional (electroretinography: ERG) analyses pigmentosa phenotype is exacerbated mutant line compared mutation alone. Indeed, observed marked ERG amplitude reduction more cell loss respect simple mutants. observations were further corroborated transcriptome analysis revealing differences between genotypes. In data, identified unique sets implicating neurogenesis, phototransduction cascade, metabolism, enhanced degeneration. Thus, our results establish dysfunction degeneration suggest underlying mechanisms, together providing new concepts for understanding managing blinding diseases.

Language: Английский

Citations

1
Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease DOI Creative Commons
Henri Leinonen, Nguyen C. Pham,

Taylor Boyd

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Sept. 10, 2020

Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon considered maladaptive and may preclude vision restoration blind. However, several recent studies utilizing triggered ablation have shown adaptive responses bipolar cells expected support normal vision. Whether such homeostatic occurs during progressive degenerative disease help maintain visual behavior is unknown. We addressed issue an established mouse model Retinitis Pigmentosa caused by P23H mutation rhodopsin. show robust modulation retinal transcriptomic network, reminiscent neurodevelopmental state, potentiation rod - cell signaling following Additionally, we found highly sensitive night mice even when more than half photoreceptors were lost. These results suggest adaptation leading persistent function disease.

Language: Английский

Citations

55