Effects of Glaucoma on<i>Chrna6</i>Expression in the Retina

Munguba, Gustavo C.; Geisert, Eldon E.; Williams, Robert W.; Tapia, María Isabel González; Lam, Daisy; Bhattacharya, Sanjoy K.; Lee, Richard K.

doi:10.3109/02713683.2012.724512

Cited by 12 publications

(7 citation statements)

References 33 publications

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“…2E,F). While Chrna6 has been previously demonstrated as an RGC subset marker 47 , we demonstrate here the presence of Anxa6 among a subset of these Pvalb + cells, where it has not been characterized before. We also investigated the expression of four genes which were correlated with Pvalb in one dataset, but not the other.…”

Section: Resultssupporting

confidence: 49%

Molecular signatures of retinal ganglion cells revealed through single cell profiling

Laboissonniere

Goetz

Martin

et al. 2019

Sci Rep

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Retinal ganglion cells can be classified into more than 40 distinct subtypes, whether by functional classification or transcriptomics. The examination of these subtypes in relation to their physiology, projection patterns, and circuitry would be greatly facilitated through the identification of specific molecular identifiers for the generation of transgenic mice. Advances in single cell transcriptomic profiling have enabled the identification of molecular signatures for cellular subtypes that are only rarely found. Therefore, we used single cell profiling combined with hierarchical clustering and correlate analyses to identify genes expressed in distinct populations of Parvalbumin-expressing cells and functionally classified RGCs. RGCs were manually isolated based either upon fluorescence or physiological distinction through cell-attached recordings. Microarray hybridization and RNA-Sequencing were employed for the characterization of transcriptomes and in situ hybridization was utilized to further characterize gene candidate expression. Gene candidates were identified based upon cluster correlation, as well as expression specificity within physiologically distinct classes of RGCs. Further, we identified Prph, Ctxn3, and Prkcq as potential candidates for ipRGC classification in the murine retina. The use of these genes, or one of the other newly identified subset markers, for the generation of a transgenic mouse would enable future studies of RGC-subtype specific function, wiring, and projection.

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Section: Resultssupporting

confidence: 49%

Molecular signatures of retinal ganglion cells revealed through single cell profiling

Laboissonniere

Goetz

Martin

et al. 2019

Sci Rep

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“…For the in situ hybridization, we examined retinas 2 days after ONC (Figure 3B) and compared it to uninjured control retinas (Figure 3A). Using the Affymetrix 2-plex Quantigene View RNA ISH Tissue Assay kit, we labeled cells expressing the RGC marker Chrna6 blue and Sox11 red (Figure 3) (Munguba et al, 2013). In the control retina, many of the cells in the ganglion cell layer were heavily labeled for Chrna6 , and a few of the cells expressed marginal levels of Sox11 .…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, we demonstrate that Sox11 is upregulated following retinal injury. For RGCs, there are many known markers, such as: Chrna6, Pou4f1, Tubb3, Thy1 , or Sncg (Barnstable and Drager, 1984; Gan et al, 1996; Mu et al, 2004; Surgucheva et al, 2008; Prasov and Glaser, 2012; Jiang et al, 2013; Munguba et al, 2013). Using these marker genes, we performed a meta-analysis of their expression in injured and uninjured retinas.…”

Section: Discussionmentioning

confidence: 99%

“…Advances in our ability to monitor molecular changes in neurons have led to an increased understanding of the events that transpire following neuronal injury (Howell et al, 2011; Moore and Goldberg, 2011; Vazquez-Chona and Geisert, 2012; Munguba et al, 2013; Templeton et al, 2013). After axonal damage, the initial response of a central nervous system (CNS) neuron may be similar to that of a neuron in the peripheral nervous system (PNS) (Carlstedt, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Different Effect of Sox11 in Retinal Ganglion Cells Survival and Axon Regeneration

Struebing

Wang

et al. 2018

Front. Genet.

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Purpose: The present study examines the role of Sox11 in the initial response of retinal ganglion cells (RGCs) to axon damage and in optic nerve regeneration in mouse.Methods: Markers of retinal injury were identified using the normal retina database and optic nerve crush (ONC) database on GeneNetwork2 (www.genenetwork.org). One gene, Sox11, was highly upregulated following ONC. We examined the role of this transcription factor, Sox11, following ONC and optic nerve regeneration in mice. In situ hybridization was performed using the Affymetrix 2-plex Quantigene View RNA In Situ Hybridization Tissue Assay System. Sox11 was partially knocked out by intravitreal injection of AAV2-CMV-Cre-GFP in Sox11f/f mice. Optic nerve regeneration model used Pten knockdown. Mice were perfused and the retinas and optic nerves were dissected and examined for RGC survival and axon growth.Results: Sox11 was dramatically upregulated in the retina following ONC injury. The level of Sox11 message increased by approximately eightfold 2 days after ONC. In situ hybridization demonstrated low-level Sox11 message in RGCs and cells in the inner nuclear layer in the normal retina as well as a profound increase in Sox11 message within the ganglion cells following ONC. In Sox11f/f retinas, partially knocking out Sox11 significantly increased RGC survival after ONC as compared to the AAV2-CMV-GFP control group; however, it had little effect on the ability of axon regeneration. Combinatorial downregulation of both Sox11 and Pten resulted in a significant increase in RGC survival as compared to Pten knockdown only. When Pten was knocked down there was a remarkable increase in the number and the length of regenerating axons. Partially knocking out Sox11 in combination with Pten deletion resulted in a fewer regenerating axons.Conclusion: Taken together, these data demonstrate that Sox11 is involved in the initial response of the retina to injury, playing a role in the early attempts of axon regeneration and neuronal survival. Downregulation of Sox11 aids in RGC survival following injury of optic nerve axons, while a partial knockout of Sox11 negates the axon regeneration stimulated by Pten knockdown.

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“…Previous ONC studies have observed changes in gene expression within the retina [ 22 , 46 , 90 - 93 ] and glial based responses within the ON [ 29 ]. Analyzing the retina and ON simultaneously allowed the identification of individual clusters related to neuronal loss and regenerative failure within each tissue separately as well as allowed us to observe the temporal response of gene expression occurring in both the ON and retina with progressive injury to these two tissues.…”

Section: Discussionmentioning

confidence: 99%

Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice

Sharma

McDowell

Liu

et al. 2014

Mol Neurodegeneration

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BackgroundCentral nervous system (CNS) trauma and neurodegenerative disorders trigger a cascade of cellular and molecular events resulting in neuronal apoptosis and regenerative failure. The pathogenic mechanisms and gene expression changes associated with these detrimental events can be effectively studied using a rodent optic nerve crush (ONC) model. The purpose of this study was to use a mouse ONC model to: (a) evaluate changes in retina and optic nerve (ON) gene expression, (b) identify neurodegenerative pathogenic pathways and (c) discover potential new therapeutic targets.ResultsOnly 54% of total neurons survived in the ganglion cell layer (GCL) 28 days post crush. Using Bayesian Estimation of Temporal Regulation (BETR) gene expression analysis, we identified significantly altered expression of 1,723 and 2,110 genes in the retina and ON, respectively. Meta-analysis of altered gene expression (≥1.5, ≤-1.5, p < 0.05) using Partek and DAVID demonstrated 28 up and 20 down-regulated retinal gene clusters and 57 up and 41 down-regulated optic nerve clusters. Regulated gene clusters included regenerative change, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. Expression of selected genes (Vsnl1, Syt1, Synpr and Nrn1) from retinal and ON neuronal clusters were quantitatively and qualitatively examined for their relation to axonal neurodegeneration by immunohistochemistry and qRT-PCR.ConclusionA number of detrimental gene expression changes occur that contribute to trauma-induced neurodegeneration after injury to ON axons. Nrn1 (synaptic plasticity gene), Synpr and Syt1 (synaptic vesicle fusion genes), and Vsnl1 (neuron differentiation associated gene) were a few of the potentially unique genes identified that were down-regulated spatially and temporally in our rodent ONC model. Bioinformatic meta-analysis identified significant tissue-specific and time-dependent gene clusters associated with regenerative changes, synaptic plasticity, axonogenesis, neuron projection, and neuron differentiation. These ONC induced neuronal loss and regenerative failure associated clusters can be extrapolated to changes occurring in other forms of CNS trauma or in clinical neurodegenerative pathological settings. In conclusion, this study identified potential therapeutic targets to address two key mechanisms of CNS trauma and neurodegeneration: neuronal loss and regenerative failure.

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Effects of Glaucoma onChrna6Expression in the Retina

Cited by 12 publications

References 33 publications

Molecular signatures of retinal ganglion cells revealed through single cell profiling

Molecular signatures of retinal ganglion cells revealed through single cell profiling

Different Effect of Sox11 in Retinal Ganglion Cells Survival and Axon Regeneration

Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice

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