Ontology highlight
ABSTRACT:
PROVIDER: PRJNA754116 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15459209_1.fastq.gz | Fastqsanger.gz | |||
| SRR15459209_2.fastq.gz | Fastqsanger.gz | |||
| SRR15425310_1.fastq.gz | Fastqsanger.gz | |||
| SRR15425310_2.fastq.gz | Fastqsanger.gz | |||
| SRR15459210_1.fastq.gz | Fastqsanger.gz |
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Project description:Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl in mice (Nrl-/-) results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl-/- retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinned but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of stress response and inflammation genes, implying their involvement in cone death. The Nrl-/- retina illustrates the long-term viability of cones in the absence of rods and may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula. Targets were generated from a pair of retinas (one Nrl-/- mouse) per biological replicate. Four biological replicates were generated for each of the five aging timepoints (1, 2, 4, 6, and 10 months post natal).
2011-11-15 | E-GEOD-33674 | biostudies-arrayexpress
Project description:The human retina has unique features that are not all fully replicated in animal models. Several human-specific features center on cone photoreceptors such as a cone-rich fovea, three cone types, and the cone precursor’s proliferative response to RB1 loss. Prior droplet-based single cell RNA-sequencing (scRNA-seq) datasets have not clearly defined cone precursor developmental states or gene expression patterns. To further elucidate photoreceptor developmental trajectories, we FACS-enriched cone and rod precursors and retinal progenitor cells from eighteen Fetal Week 13-19 retina and performed deep, full-length scRNA-seq. These data were used to evaluate post-mitotic photoreceptor precursor trajectories, accompanying gene expression changes, and cone-specific features that drive the cone precursor proliferative response.
2023-01-01 | GSE207802 | GEO
Project description:Cone photoreceptors are the primary initiator of visual transduction in the human retina. Dysfunction or death of rod photoreceptors precedes cone loss in many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for cone survival. Rod differentiation and homeostasis are dependent on the basic motif leucine zipper transcription factor NRL. The loss of Nrl in mice (Nrl-/-) results in a retina with predominantly S-opsin containing cones that exhibit molecular and functional characteristics of WT cones. Here we report that Nrl-/- retina undergoes a rapid but transient period of degeneration in early adulthood, with cone apoptosis, retinal detachment, alterations in retinal vessel structure, and activation and translocation of retinal microglia. However, cone degeneration stabilizes by four months of age, resulting in a thinned but intact outer nuclear layer with residual cones expressing S- and M-opsins and a preserved photopic ERG. At this stage, microglia translocate back to the inner retina and reacquire a quiescent morphology. Gene profiling analysis during the period of transient degeneration reveals misregulation of stress response and inflammation genes, implying their involvement in cone death. The Nrl-/- retina illustrates the long-term viability of cones in the absence of rods and may serve as a model for elucidating mechanisms of cone homeostasis and degeneration that would be relevant to understanding diseases of the cone-dominant human macula.
2011-11-15 | GSE33674 | GEO
Project description:Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown.
2017-03-07 | GSE86442 | GEO
Project description:Tikidji-Hamburyan2018 - Rod phototransduction
under strong illumination
This model is described in the article:
Rods progressively escape
saturation to drive visual responses in daylight
conditions.
Tikidji-Hamburyan A, Reinhard K,
Storchi R, Dietter J, Seitter H, Davis KE, Idrees S, Mutter M,
Walmsley L, Bedford RA, Ueffing M, Ala-Laurila P, Brown TM, Lucas
RJ, Münch TA.
Nat Commun 2017 Nov; 8(1): 1813
Abstract:
Rod and cone photoreceptors support vision across large
light intensity ranges. Rods, active under dim illumination,
are thought to saturate at higher (photopic) irradiances. The
extent of rod saturation is not well defined; some studies
report rod activity well into the photopic range. Using
electrophysiological recordings from retina and dorsal lateral
geniculate nucleus of cone-deficient and visually intact mice,
we describe stimulus and physiological factors that influence
photopic rod-driven responses. We find that rod contrast
sensitivity is initially strongly reduced at high irradiances,
but progressively recovers to allow responses to moderate
contrast stimuli. Surprisingly, rods recover faster at higher
light levels. A model of rod phototransduction suggests that
phototransduction gain adjustments and bleaching adaptation
underlie rod recovery. Consistently, exogenous chromophore
reduces rod responses at bright background. Thus, bleaching
adaptation renders mouse rods responsive to modest contrast at
any irradiance. Paradoxically, raising irradiance across the
photopic range increases the robustness of rod responses.
This model is hosted on
BioModels Database
and identified by:
MODEL1710030000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
| MODEL1710030000 | BioModels
Project description:The macula of the retina has a high ratio of cones to rods and is critical for central vision and visual acuity. Here we report the generation, transcriptome profiling, and functional validation of single cells from cone-enriched human retinal organoids differentiated from hESCs. Single-cell RNA-seq of 8-month retinal organoids identified clusters of cone and rod photoreceptors and confirmed the cone enrichment initially revealed by immunostaining. Collectively, we have established cone-enriched retinal organoids and a reference of transcriptomes that are rich resources for retinal studies.
2019-04-25 | GSE119343 | GEO
Project description:Regulation of photoreceptor phosphodiesterase (PDE6) activity is responsible for the speed, sensitivity, and recovery of the photoresponse during visual signaling in vertebrate photoreceptor cells. It is hypothesized that the physiological differences in the light responsiveness of rods and cones may result in part from differences in the structure and regulation of the distinct isoforms of rod and cone PDE6. Although rod and cone PDE6 catalytic subunits share a similar domain organization consisting of tandem GAF domains (GAFa and GAFb) and a catalytic domain, cone PDE6 is a homodimer whereas rod PDE6 consists of two homologous catalytic subunits. Here we provide the x-ray crystal structure of cone GAFab regulatory domain solved at 3.3 Å resolution, in conjunction with chemical cross-linking and mass spectrometric analysis of conformational changes to GAFab induced upon binding of cGMP and the PDE6 inhibitory γ-subunit (Pγ). Ligand-induced changes in cross-linked residues implicate multiple conformational changes in the GAFa and GAFb domains in forming an allosteric communication network that communicates with the PDE6 catalytic domains. Molecular dynamics (MD) simulations of cone GAFab revealed asymmetry in the two GAFab subunits forming the homodimer and allosteric perturbations on cGMP binding. Cross-linking of Pγ to GAFab in conjunction with solution NMR spectroscopy of isotopically labeled Pγ identified the central polycationic region of Pγ interacting with the GAFb domain. These results provide a mechanistic basis for developing allosteric activators of PDE6 with therapeutic implications for halting the progression of several retinal degenerative diseases.
2022-02-15 | PXD020817 | Pride
Project description:Photoreception, a form of sensory experience, is essential for normal development of the mammalian visual system. Detecting photons during development is a prerequisite for visual system function - from shaping vision’s first synapse and maturation of retinal vascular networks, to transcriptional establishment and maturation of cell types within the visual cortex. Consistent with this theme, we find that the lighting environment regulates developmental rod photoreceptor apoptosis via OPN4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Using a combination of genetics, sensory environment manipulations, and computational approaches, we establish a molecular pathway in which light-dependent glutamate release from ipRGCs is detected via a transiently expressed kainate receptor (GRIK3) in rod precursors localized to the inner retina. Communication between ipRGCs and nascent inner retinal rods appears to be mediated by transient hybrid neurites projecting from ipRGCs that sense light before eye-opening. These structures, previously referred to as outer retinal dendrites (ORDs), span the ipRGC-rod precursor distance over the first postnatal week and contain the machinery for sensory detection (melanopsin, OPN4) and anterograde neurotransmitter release (Synaptophysin and VGLUT2). Computational and histological assessment of human mid-gestation development reveal conservation of several hallmarks of an ipRGC-to-rod precursor pathway, including displaced rod precursors, transient GRIK3 expression in the rod lineage, and the presence of ipRGCs with putative neurites projecting deep into the developing human retina. Thus, this analysis defines a retinal retrograde signaling pathway that links the sensory environment to rod precursors via ipRGC photoreceptors, allowing the visual system to adapt to distinct lighting environments prior to eye-opening.
2024-07-04 | GSE269102 | GEO