A cell atlas of the chick retina based on single-cell transcriptomics

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Jan. 4, 2021

Retinal structure and function have been studied in many vertebrate orders, but molecular characterization has largely confined to mammals. We used single-cell RNA sequencing (scRNA-seq) generate a cell atlas of the chick retina. identified 136 types plus 14 positional or developmental intermediates distributed among six classes conserved across vertebrates – photoreceptor, horizontal, bipolar, amacrine, retinal ganglion, glial cells. To assess morphology molecularly defined types, we adapted method for CRISPR-based integration reporters into selectively expressed genes. For Müller glia, found that transcriptionally distinct cells were regionally localized along anterior-posterior, dorsal-ventral, central-peripheral axes. also immature horizontal cell, oligodendrocyte persist late embryonic stages. Finally, analyzed relationships chick, mouse, primate types. Our results provide foundation anatomical, physiological, evolutionary, studies avian visual system.

Language: Английский

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Preservation of vision after CaMKII-mediated protection of retinal ganglion cells

Cell, Journal Year: 2021, Volume and Issue: 184(16), P. 4299 - 4314.e12

Published: July 22, 2021

Language: Английский

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Analytic Pearson residuals for normalization of single-cell RNA-seq UMI data

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: Sept. 6, 2021

Standard preprocessing of single-cell RNA-seq UMI data includes normalization by sequencing depth to remove this technical variability, and nonlinear transformation stabilize the variance across genes with different expression levels. Instead, two recent papers propose use statistical count models for these tasks: Hafemeister Satija (Genome Biol 20:296, 2019) recommend using Pearson residuals from negative binomial regression, while Townes et al. 20:295, fitting a generalized PCA model. Here, we investigate connection between approaches theoretically empirically, compare their effects on downstream processing.We show that model produces noisy parameter estimates because it is overspecified, which why original paper employs post hoc smoothing. When specified more parsimoniously, has simple analytic solution equivalent rank-one Poisson GLM-PCA Further, our analysis indicates per-gene overdispersion in are biased, fact consistent being independent gene expression. We then control without biological variability estimate counts, find several experimental protocols, close suggest very moderate overdispersion. Finally, perform benchmark performance residuals, variance-stabilizing transformations, scRNA-seq datasets known ground truth.We demonstrate strongly outperform other methods identifying biologically variable genes, capture meaningful variation when used dimensionality reduction.

Language: Английский

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Overlapping transcriptional programs promote survival and axonal regeneration of injured retinal ganglion cells

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2625 - 2645.e7

Published: June 28, 2022

Language: Английский

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Neuroinflammation, Microglia and Implications for Retinal Ganglion Cell Survival and Axon Regeneration in Traumatic Optic Neuropathy

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 4, 2022

Traumatic optic neuropathy (TON) refers to a pathological condition caused by direct or indirect insult the nerves, which often leads partial permanent vision deficit due massive loss of retinal ganglion cells (RGCs) and their axonal fibers. Retinal microglia are immune-competent residing in retina. In rodent models nerve crush (ONC) injury, resident gradually become activated, form end-to-end alignments vicinity degenerating RGC axons, actively internalized them. Some activated adopt an amoeboid morphology that engulf dying RGCs after ONC. injured nerve, contribute myelin debris clearance at lesion site. However, phagocytic capacity is extremely poor therefore cellular largely ineffective. The presence growth-inhibitory glial scar formed reactive astrocytes inhibit regeneration accounts for visual function recovery patients with TON. this Review, we summarize current understanding survival axon Resident play key role facilitating Wallerian degeneration subsequent they also responsible producing pro-inflammatory cytokines, chemokines, oxygen species possess neurotoxic effects on RGCs. Intraocular inflammation triggers influx blood-borne myeloid produce oncomodulin promote regeneration. intraocular induces chronic neuroinflammation exacerbates secondary tissue damages limits Activated required proliferation oligodendrocyte precursor (OPCs); however, sustained activation suppress differentiation OPCs into mature oligodendrocytes remyelination injury. Collectively, controlled infiltrating facilitate repair. Recent advance single-cell RNA-sequencing identification microglia-specific markers could improve our microglial biology development novel therapeutic strategies aiming switch microglia’s phenotype foster neuroprotection.

Language: Английский

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Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells

Neuron, Journal Year: 2022, Volume and Issue: 110(16), P. 2607 - 2624.e8

Published: June 28, 2022

Language: Английский

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Evolution of neuronal cell classes and types in the vertebrate retina

Nature, Journal Year: 2023, Volume and Issue: 624(7991), P. 415 - 424

Published: Dec. 13, 2023

Abstract The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs 1 . Retinal cell types may have evolved to accommodate these varied needs, but this has not been systematically studied. Here we generated and integrated single-cell transcriptomic atlases from 17 species: humans, two non-human primates, four rodents, three ungulates, opossum, ferret, tree shrew, a bird, reptile, teleost fish lamprey. We found high molecular conservation six retinal classes (photoreceptors, horizontal cells, bipolar amacrine ganglion cells (RGCs) Müller glia), with variation related evolutionary distance. Major subclasses were also conserved, whereas among within or was more pronounced. However, an integrative analysis revealed that numerous are shared species, based on gene expression programmes likely trace back early ancestral vertebrate. degree increased outer (photoreceptors) inner (RGCs), suggesting evolution acts preferentially shape output. Finally, identified rodent orthologues midget RGCs, which comprise than 80% RGCs human retina, subserve high-acuity vision, previously believed be restricted primates 2 By contrast, mouse large receptive fields around 2% RGCs. Projections both primate orthologous overrepresented thalamus, supplies primary cortex. suggest innovations, descendants evolutionarily ancient decreased size number as evolved, thereby facilitating acuity cortical processing information.

Language: Английский

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Latent epigenetic programs in Müller glia contribute to stress and disease response in the retina

Developmental Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Systemic TRPV4 inhibition worsens retinal response to acute intraocular pressure elevation in older but not younger mice

Optometry and Vision Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Previous evidence showed that transient receptor potential vanilloid 4 (TRPV4) inhibition was protective of retinal ganglion cell (RGC) loss after chronic intraocular pressure (IOP) elevation in young animals. However, the role TRPV4 mechanosensing IOP changes aging eye is not well understood. This study compared recovery function and structure acute 3- 12-month-old mouse eyes with without inhibition. We examined expression 2-month-old rodent using immunohistochemistry transcript analysis isolated macroglia RGCs. To modulate TRPV4, mice were treated daily either vehicle or a antagonist (HC-067047 10 mg/kg) delivered intraperitoneally for 7 days before (50 mmHg 30 minutes). Retinal assessed dark-adapted full-field electroretinography optical coherence tomography, respectively. Müller cells strongly expressed TRPV4. Seven elevation, RGC functional significantly poorer older age-matched controls (-54 ± 7% vs. -24 10%, p=0.046) their younger antagonist-treated counterparts (-5 5%, p<0.001). there an age-related deficit from

Language: Английский

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Extracellular vesicle therapy for retinal diseases

Progress in Retinal and Eye Research, Journal Year: 2020, Volume and Issue: 79, P. 100849 - 100849

Published: March 10, 2020

Language: Английский

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