Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-invasive electrical stimulation restores corneal nerve density and sensory function in diabetic neuropathy via KCNN-dependent mechanism

ABSTRACT: Corneal nerve, originated from trigeminal ganglia, play an important role in conreal sensation and homeotasis. Under disease conditions when corneal nerves are damaged, such as diabetes, corneal injury, or eye surgury, patients suffer from dry eye, pain, delayed wound healing, or urceration. Current treatments are limited, underscoring the need for a regenerative therapy. Here we show that a non-invasive neural modulation therapy, transcutaneous electrical stimulation (ES), significantly restore the nerve density and sensory function in both streptozotocin-induced diabetes mice and keratectomy model. This transcriptomics analysis of TGs from in vivo ES in keratectomy models aims to find mechanistic insights into the ES-induced corneal reinnervation. The results point to ion transport and Ca2+ signaling alteration, alongside activation of neural regeneration pathways. Consistently, membrane potential recording in TGs shows a rapid hyperpolarization upon ES accompanied by increased [Ca2+]i level. Inhibition of potassium intermediate/small conductance calcium-activated channel (KCNN) abolishes the hyperpolarization and neural regeneration effect, whereas activation of KCNN channel significantly enhances nerve regeneration in the STZ model compared with sham treatment. Overall, ES restores corneal nerve density and function via KCNN activation in a diabetic mouse model, offering a novel, non-invasive, and clinically translatable therapeutic strategy for diabetic neuropathy.

ORGANISM(S): Mus musculus

PROVIDER: GSE330561 | GEO | 2026/07/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy

Project description:Neurotrophic Keratopathy (NK),classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe speciﬁc medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative to the neurotization surgery. However, few studies have been conducted to the molecular mechanism underlying the response to the treatment. Here, we carried out tears proteomics to highlight the protein expression during pharmacological treatment of NK. Our data emphasized a proteome modulation duringrhNGF treatment related to an increase in DNA synthesis, an activation ofboth BDNF signaland IL6 receptor.Furthermore, the amount of neuronal Extracellular Vesicles EVs (CD171+)correlated with the EVs carrying IL6R (CD126+) togetherassociated to the inflammatory EVs (CD45+) in tears. Such scenario determined drug response, confirmed by an in vivo confocal microscopy analysis, showing an increase in length, density and number of nerve fiber branches during treatment. In summary, rhNGF treatment seems to determine an inflammatory micro-environment, mediated by functionalized EVs, defining the drug response by stimulating protein synthesis and fiber regeneration.

2022-02-14 | PXD025408 | Pride

Gene expression timecourse in zebrafish whole eye in response to optic nerve crush

Project description:It is well-established that neurons in the adult mammalian central nervous system are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX), retinal ganglion cells (RGC) regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after optic nerve crush can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. We used microarrays to detail the global gene expression patterns underlying a successful regeneration or the optic nerve following injury. Experiment Overall Design: Microarray analysis was performed on total RNA extracted from whole eye following optic nerve crush (ONX) or sham surgery at defined intervals (4, 12, & 21 days).

2010-02-21 | E-GEOD-19298 | biostudies-arrayexpress

Novel RvD6 stereoisomer induces corneal nerve regeneration and wound healing post-injury by modulating trigeminal transcriptomic signature

Project description:We performed the RNA-seq analysis to unravel the underlying mechanism of corneal nerve regeneration after treatment with our identified RvD6 isomer and RvD6 standard.

2020-03-18 | GSE138685 | GEO

dsRNA induced IFNβ-MMP13 axis drives corneal wound healing

Project description:Cornea, the outermost transparent layer of the eye, is the first line of defense against external threats. Following injury, the wound healing response is crucial to corneal repair and regeneration, yet its underlying mechanism is poorly understood. Our study was designed to investigate the role of dsRNA and its regulatory network in corneal wound healing.

2022-02-05 | GSE191228 | GEO

Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration [miRNA-seq]

Project description:Diabetes mellitus (DM) is a complex metabolic disorder. Long-term hyperglycemia may induce diabetic keratopathy (DK), which is mainly characterized by delayed corneal epithelial regeneration. MicroRNAs (miRNAs) have been reported to play regulatory roles during tissue regeneration. However, the molecular mechanism by which miRNAs influence epithelial regeneration in DK is largely unknown. In this study, we performed miRNA and mRNA sequencing of regenerative corneal epithelium tissue from streptozotocin-induced type 1 diabetic (T1DM) and wild-type mice to screen for differentially expressed miRNAs and mRNAs. Based on regulatory network analysis, miR-223-5p was selected for subsequent experiments and Hpgds was then identified as a direct target gene. MiR-223-5p downregulation significantly promoted diabetic corneal epithelial wound healing and nerve regeneration. However, the beneficial effects of miR-223-5p inhibition were abolished by an Hpgds inhibitor. Furthermore, mechanistic studies demonstrated that miR-223-5p suppression ameliorated inflammation and enhanced cell proliferation signaling in DK. Taken together, our findings revealed that the regulatory role of miR-223-5p in diabetic corneal epithelial and nerve regeneration by mediating inflammatory processes and cell proliferation signaling. And silencing miR-223-5p may contribute to the development of potential therapeutic strategies for DK.

2021-08-23 | GSE180493 | GEO

Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration [RNA-seq]

2021-08-23 | GSE180490 | GEO

Developmental and Injury-induced Changes in DNA Methylation in Regenerative versus Non-regenerative Regions of the Vertebrate (Xenopus laevis) Central Nervous System assayed by 5hmC MeDIP and by ChIP-seq for Histone Markers

Project description:Xenopus is uniquely suited for identifying core features of successful CNS axon regeneration, because parts of its CNS (e.g., eye), regenerate axons throughout life, whereas others (e.g., hindbrain) do so only as tadpoles. To aid in the interpretation of bisulfite whole genome methylation sequencing (WGBS) on juvenile frog eye after optic nerve injury, and on hindbrain samples from tadpole and juvenile frog after spinal cord injury during the peak phase of axon regeneration, we performed ChIP-seq for histone modifications associated with active gene expression (H3K4me3 & H3K27ac) and repressed gene expression (H3K27me3 & H3K9me3) on these same tissues, as well as DNA-immunoprecipitation sequencing (DIP seq) for 5-hydroxymethyl cytosine (5hmC) on eye samples during optic nerve regeneration.

2022-01-05 | GSE183350 | GEO

Comparison of Trabecular Meshwork-Derived Cells (TMDCs) with other somatic Cell Types

Project description:Microarray study comparing trabecular meshwork-derived cells (TMDCs) from the iridocorneal angle of the human eye, with other human cell types such as scleral fibroblasts, corneal fibroblasts, retinal pigmented epithelial (RPE) cells, corneal stroma, human embryonic stem cells (hESC), neural precursors differentiated from hESC, human umbilical vein endothelial (HUVEC) cells and human adipose-tissue-derived mesenchymal stromal cells (MSC)

2012-05-01 | GSE28679 | GEO

α7 Nicotinic Acetylcholine Receptor Regulates Macrophage-Mediated Neuroinflammation in Dry Eye Disease

Project description:Patients with dry eye disease (DED) often exhibit neurological abnormalities and may even suffer from neuropathic pain and pain-related anxiety or depression. However, addressing nerve abnormalities in DED remains a formidable challenge, as current therapies fail to halt disease progression. Our study found that activating α-7 nicotinic acetylcholine receptor (α7nAChR), a pivotal regulator in the anti-inflammatory pathway connecting the nervous and immune systems, effectively restores corneal epithelium integrity and enhances nerve sensitivity in DED, pointing to its promising therapeutic potential. Furthermore, we have revealed that α7nAChR stimulates genes involved in immune-mediated inflammatory progression and neuroregulation, inhibits the expression of transient receptor potential vanilloid-1 (TRPV1), reinstates corneal nerve density, and alleviates anxiety-like behaviors associated with severe DED by downregulating the proportion of CD86+ M1 macrophages (pro-inflammatory phenotypes). In summary, our findings underscore the activation of α7nAChR as a pioneering therapeutic approach for preserving corneal nerves balance and controlling inflammation in DED.

2024-04-07 | GSE263136 | GEO

Differential gene expression in Danio rerio during optic nerve regeneration

Project description:To gain a better understanding of the factors necessary for successful CNS regeneration, a temporal analysis of the changes in gene expression in the eye caused by optic nerve injury was conducted. Dual color oligonucleotide microarrays were used to compare total RNA harvested from the eyes of sham-operated and optic nerve-injured fish at 3, 24, and 168 hours following surgery. Optic nerve injured fish are compared to sham-operated fish in order to eliminate gene expression due to non-neuronal damage and inflammatory response. Statistical analyses identified 131 genes with a 2.0-fold or greater difference in expression. Wild type zebrafish were obtained from a local pet store. Optic nerve injury was conducted using a severing model accomplished as follows. Zebrafish were anesthetized in 0.2% MS-222 dissolved in tank water. The muscles surrounding the eye were cut and the eye angled rostrally to expose the nerve. The optic nerve was then severed using microsissors without damaging the ophthalmic artery. In sham operated fish the muscles surrounding the eye were severed but the nerve was not damaged. RNA was extracted from the eye at three time points following surgery 3 hours, 24 hours, and 168 hours. RNA was pooled from multiple fish to achieve 10 ug total RNA. Samples were collected in triplicate per time point. Gene expression was analyzed on a dual color oligonucleotide array where the optic nerve injured fish were compared to sham-operated fish. Four samples of RNA were also collected from control fish and compared to each other on the microarray to confirm that processing did not create expression differences.

2010-05-16 | E-GEOD-17854 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data