Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA941790 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23725122_1.fastq.gz | Fastqsanger.gz | |||
| SRR23725122_2.fastq.gz | Fastqsanger.gz | |||
| SRR23725123_1.fastq.gz | Fastqsanger.gz | |||
| SRR23725123_2.fastq.gz | Fastqsanger.gz | |||
| SRR23725124_1.fastq.gz | Fastqsanger.gz |
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Project description:A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and in human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and on separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.
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Project description:The optic nerve is a white matter tract that conveys visual information to the brain. A detailed investigation of the proteome of the normal human retrobulbar optic nerve may help facilitate studies of the biology and pathophysiology of the optic nerve. We conducted an in-depth proteomic analysis of optic nerve from five adults. Proteins were fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. We identified 2,711 non-redundant proteins in the human retrobulbar optic nerve, including the astrocytic marker glial fibrillary acidic protein, several proteins expressed by oligodendrocytes (laminin, proteolipid protein, and fibronectin), myelin proteins (myelin basic protein, myelin-associated glycoprotein), paranodal structural proteins (neurofascin, contactin, α, β, and γ adducins, septin 2, endophilin, ankyrin β, spectrin), proteins involved in neuronal protection and regeneration (α crytallins A and B, dedicator of cytokinesis proteins, ciliary neurotrophic factor), proteins associated with open-angle glaucoma (thioredoxin, heat shock protein-70), and proteins associated with optic neuritis (aquaporin-4). Twenty-one unambiguous protein isoforms were identified in the optic nerve.
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