Aging Reprograms the Rhythmic Transcriptome in the Retina
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE300500 | GEO | 2025/06/24
REPOSITORIES: GEO
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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:Chronic ocular inflammation is associated with many retinal degenerative diseases that result in vision loss. The immune-privileged environment and complex organization of retinal tissue allow for the retina’s essential role in visual function processes, yet confound inquiries into cell-specific inflammatory effects that lead to retinal dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in many retinal cell populations and has been implicated in retinal immune regulation. However, the direction (i.e., promotion or inhibition) in which Cav1 regulates inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion in the retina paradoxically resulted in reduced retinal inflammatory cytokine production with concurrent elevated retinal immune cell infiltration. We hypothesized that our previous results could be explained by cell-specific Cav1 functions in the retina. Here, we utilized our Chx10 (visual system homeobox 2)-Cre knockout model to deplete Cav1 specifically in the neural retinal (NR) compartment in order to clarify the role of neural retinal-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal LPS (lipopolysaccharide) challenge. Our data support that neural retinal-derived Cav1 promotes retinal tissue inflammation as Chx10-mediated Cav1 depletion was sufficient to suppress both retinal cytokine production and immune cell infiltration following inflammatory stimulation. Additionally, we identify Traf3 (tumor necrosis factor (TNF) receptor-associated factor 3) as a highly expressed potential immune modulator in retinal tissue that is upregulated with NR-Cav1 depletion. Furthermore, this study highlights the importance for understanding the role of Cav1 (and other proteins) in cell-specific contexts.
2021-09-08 | PXD016872 | Pride
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:Aging Reprograms the Rhythmic Transcriptome in the Retina
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Project description:We discovered that Bmal1 knockdown in retinal microglia alters their diurnal clock gene expression, inflammatory gene expression, and morphology. Furthermore, we found that this disruption of diurnal physiology in microglia results in reduced scotopic visual function, retinal neurodegeneration, and abnormal wheel running behavior in mice, suggesting that maintenance of the microglial clock contributes to retinal homeostasis. Subsequently, we investigated transcriptional alterations in retinal microglia and non-microglial cells in the retina to uncover gene expression patterns that may explain these clock-dependent phenotypes and potentially identify homeostatic neuro-glial signaling mechanisms dependent on microglial clock biology.
2025-07-28 | GSE282175 | GEO
Project description:The mammalian central nervous system (CNS) and its retina are susceptible to age-related patholgoies, resulting in progressive, irreversible diseases like glaucoma and age-related macular degeneration (AMD), which are increasingly prevalent with rising life expectancy. Currently, there are no targeted long-term therapies to prevent vision loss. The short lived African turquoise killifsh (Nothobranchius furzeri, GRZ-AD) is a valuable genetic model for ageing studies, displaying rapid ageing phenotypes within its four to six-month lifespan. Our investigation on the molecular consequences of ageing in the retina, employing scRNA-sequencing, shows a a comprehensive overview of the cellular heterogeneity of the killifish retina, uncovering age-related gene expression changes specific to certain retinal cell populations.
2024-08-21 | GSE255364 | GEO
Project description:Retinal diseases often lead to degeneration of specific retinal cell types with currently limited therapeutic options to replace the lost neurons. Previous studies have reported that overexpression of ASCL1 or combinations of proneural factors in Müller glia (MG) induces regeneration of functional neurons in the adult mouse retina. Recently, we applied the same strategy in dissociated cultures of fetal human MG and although we stimulated neurogenesis from MG, our effect in 2D cultures was modest and our analysis of newborn neurons was limited. In this study, we aimed to improve our MG reprogramming strategy in a more intact retinal environment. For this purpose, we used an in vitro culture system of human fetal retinal tissue and adult human postmortem retina. To stimulate reprogramming, we used lentiviral vectors to deliver constructs with a glial-specific promoter (HES1) driving ASCL1 alone or in combination with additional developmental transcription factors such as ATOH1 and NEUROD1. Combining IHC, scRNA-seq and electrophysiology, we show for the first time that human MG can generate new neurons even in adults. This work constitutes a key step towards a future clinical application of this regenerative medicine approach for retinal degenerative disorders.
2024-12-13 | GSE284180 | GEO
Project description:The retina is a delicate tissue that detects light, converts photochemical energy into neural signals, and transmits the signals to the visual cortex of the brain. A detailed protein inventory of the proteome of the normal human eye may provide a foundation for new investigations into both the physiology of the retina and the pathophysiology of retinal diseases. To provide an inventory, proteins were extracted from five retinas of normal eyes and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed in duplicate using LC-MS/MS on an Orbitrap Elite mass spectrometer. A total of 3,436 non-redundant proteins were identified in the human retina, including 20 unambiguous protein isoforms, of which 8 have not previously been demonstrated to exist at the protein level. The proteins identified in the retina included most of the enzymes involved in the visual cycle and retinoid metabolism. One hundred and fifty-eight proteins that have been associated with age-related macular degeneration were identified in the retina. The MS proteome database of the human retina may serve as a valuable resource for future investigations of retinal biology and disease.
2016-02-26 | MSV000079537 | MassIVE
Project description:Objective: To determine the effects of age and topographic location on gene expression in human neural retina. Methods: Macular and peripheral neural retina RNA were isolated from human donor eyes for DNA microarray and quantitative RTPCR analyses. Results: Total RNA from human donor retina preserved integrity. Hierarchic clustering analysis demonstrates the gene expression profiles of young, old, macula and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young or old retina are identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10 and SFRP2) shown preferably expressed in the periphery. Conclusions: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases. Twleve youang and older retinal macular or prepheral RNA samples are used for DNA microarray study to compare the effects of aging and anatomic location on gene expression in human retina.
2015-05-27 | E-GEOD-32614 | biostudies-arrayexpress
Project description:The retina is a delicate tissue that detects light, converts photochemical energy into neural signals, and transmits the signals to the visual cortex of the brain. A detailed protein inventory of the proteome of the normal human eye may provide a foundation for new investigations into both the physiology of the retina and the pathophysiology of retinal diseases. To provide an inventory, proteins were extracted from five retinas of normal eyes and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed in duplicate using LC-MS/MS on an Orbitrap Elite mass spectrometer. A total of 3,436 non-redundant proteins were identified in the human retina, including 20 unambiguous protein isoforms, of which 8 have not previously been demonstrated to exist at the protein level. The proteins identified in the retina included most of the enzymes involved in the visual cycle and retinoid metabolism. One hundred and fifty-eight proteins that have been associated with age-related macular degeneration were identified in the retina. The MS proteome database of the human retina may serve as a valuable resource for future investigations of retinal biology and disease.
2014-11-27 | PXD001242 | Pride