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Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells

ABSTRACT: Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells

PROVIDER: PRJNA486790 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7721800.fastq.gz	Fastqsanger.gz
	SRR7721810.fastq.gz	Fastqsanger.gz
	SRR7721820.fastq.gz	Fastqsanger.gz
	SRR7721830.fastq.gz	Fastqsanger.gz
	SRR7721840.fastq.gz	Fastqsanger.gz

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Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells

Project description:Purpose: The goal of this study was to determine a “molecular parts list” for intrinsically photosensitive retinal ganglion cells (ipRGCs), which are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. Methods: We conducted a thorough unbiased transcriptomic analysis of ipRGCs by purifying GFP-tagged ipRGCs through a combination of FACS and immunoaffinity and comparing this the transcriptional profile of GFP-negative RGCs. We did this in two different mouse lines, marking partially overlapping subsets of ipRGCs. One was a BAC transgenic reporter (Opn4-GFP), which fluorescently labels M1-M3 ipRGCs and the other was a Opn4-Cre;Z/EG reporter system, which labels all ipRGC subtypes, M1-M6 Results: We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are unexpectedly diverse at the molecular level. Conclusions: Our study represents the first detailed analysis of ipRGC transcriptomes by RNA-seq. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes.

2019-08-15 | GSE118780 | GEO

Transcriptomic Signatures of Postnatal and Adult Intrinsically Photosensitive Ganglion Cells.

Project description:Intrinsically photosensitive retinal ganglion cells (ipRGCs) are rare mammalian photoreceptors essential for non-image-forming vision functions, such as circadian photoentrainment and the pupillary light reflex. They comprise multiple subtypes distinguishable by morphology, physiology, projections, and levels of expression of melanopsin (Opn4), their photopigment. The molecular programs that distinguish ipRGCs from other ganglion cells and ipRGC subtypes from one another remain elusive. Here, we present comprehensive gene expression profiles of early postnatal and adult mouse ipRGCs purified from two lines of reporter mice that mark different sets of ipRGC subtypes. We find dozens of novel genes highly enriched in ipRGCs. We reveal that Rasgrp1 and Tbx20 are selectively expressed in subsets of ipRGCs, though these molecularly defined groups imperfectly match established ipRGC subtypes. We demonstrate that the ipRGCs regulating circadian photoentrainment are diverse at the molecular level. Our findings reveal unexpected complexity in gene expression patterns across mammalian ipRGC subtypes.

| S-EPMC6712207 | biostudies-literature

Single-cell RNAseq data from mouse intrinsically-photosensitive retinal ganglion cells

Project description:Single-cell RNAseq data from mouse intrinsically-photosensitive retinal ganglion cells

| PRJNA931936 | ENA

Single-cell RNAseq data from mouse intrinsically-photosensitive retinal ganglion cells

Project description:The goal of this study was to characterize the transcriptomes of intrinsically-photosenstive retinal ganglion cells that innervate different retinorecipient target regions in the brain

2023-05-01 | GSE224600 | GEO

Developmental control of rod photoreceptor number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells

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

Developmental control of rod photoreceptor number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells

Project description:Developmental control of rod photoreceptor number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells

| PRJNA1120107 | ENA

PTEN inhibition dedifferentiates long-distance axon-regenerating intrinsically photosensitive retinal ganglion cells and upregulates mitochondria-associated DYNLT1A and LARS2

Project description:The central nervous system (CNS) projection neurons fail to spontaneously regenerate injured axons. Targeting the developmentally regulated genes in order to reactivate embryonic intrinsic axon growth capacity, or targeting tumor suppressor genes such as Pten, promote axon regeneration in a subset of injured retinal ganglion cells (RGCs). The subset of RGCs that regenerate axons in response to inhibition of Pten was narrowed-down to the Opn4+ intrinsically photosensitive (ip) and α subtypes of RGCs. Here, we used single cell RNA-sequencing (scRNA-seq) to investigate why only a subset of injured RGCs regenerate axons in response to Pten knockdown (KD), and to characterize the relationship between axon regeneration promoted by targeting Pten and the developmental decline in intrinsic axon growth capacity. We found that, only the most similar to embryonic state ipRGC subtypes C33 and C40 regenerated axons in response to Pten KD, which dedifferentiated them even further towards an embryonic state. We also found that genes downstream of Pten KD, specifically in the RGCs that regenerated axons, include mitochondria-associated developmentally regulated and non-developmentally regulated Dynlt1a and Lars2, respectively, which promoted axon regeneration on their own. Overall, we show that injury itself reverts transcriptome towards an embryonic state only in some neuronal subtypes and not sufficiently close to embryonic state to confer response to Pten KD, whereas certain mature neuronal subtypes are similar to embryonic state even without injury, which primes them to regenerate axons in response to Pten KD, that dedifferentiates them further towards an embryonic state and upregulates mitochondria-associated Dynlt1a and Lars2.

2023-04-11 | GSE210137 | GEO

PTEN inhibition dedifferentiates long-distance axon-regenerating intrinsically photosensitive retinal ganglion cells and upregulates mitochondria-associated DYNLT1A and LARS2

Project description:PTEN inhibition dedifferentiates long-distance axon-regenerating intrinsically photosensitive retinal ganglion cells and upregulates mitochondria-associated DYNLT1A and LARS2

| PRJNA864030 | ENA

[Intrinsically photosensitive retinal ganglion cells].

Project description:BackgroundMelanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGC) area third class of photoreceptors in the retina in addition to rods and cones. They are a small heterogeneous population of cells primarily mediating non-image-forming visual functions.ObjectiveThis article provides an overview of the current understanding of the functions and the diversity of ipRGCs. It moreover gives an insight into clinically and translationally relevant aspects and treatment options.Material and methodsNarrative review article.ResultsipRGCs make up ~1-2% of all retinal ganglion cells and are divided into 6 specialized subtypes. With the photopigment melanopsin they can trigger light responses without rod or cone input and can relay irradiance information to various centers of the brain. Depending on the subtype, ipRGCs mediate non-image-forming tasks, such as the pupillary light reflex or synchronizing the circadian clock, and image-forming tasks, such as contrast optimization. ipRGCs exhibit differential resilience against optic nerve damage, making them an interesting study object for the development of neuroprotective strategies. In addition, melanopsin is an attractive optogenetic tool for vision restoration.ConclusionKnowledge on ipRGC physiology is indispensable for understanding frequent clinical observations. Their functional and morphological features are the subject of active research, which highlights novel translational strategies.

| S-EPMC9005408 | biostudies-literature

Functional diversity of human intrinsically photosensitive retinal ganglion cells.

Project description:Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non-image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs' photoresponses. We discovered three functional ipRGC subtypes with distinct sensitivities and responses to light. The response of one ipRGC subtype appeared to depend on exogenous chromophore supply, and this response is conserved in both human and mouse retinas. Rods and cones also provided input to ipRGCs; however, each subtype integrated outer retina light signals in a distinct fashion.

| S-EPMC7120228 | biostudies-literature

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