 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 07, 2020 |
| Title |
Sub-region-Specific Optic Nerve Head Glial Activation in Glaucoma |
| Organism |
Felis catus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Glaucoma, a multifactorial neurodegenerative disease characterized by progressive loss of retinal ganglion cells and their axons in the optic nerve, is a leading cause of irreversible vision loss. Intraocular pressure (IOP) is a risk factor for axonal damage, which initially occurs at the optic nerve head (ONH). Complex cellular and molecular mechanisms involved in the pathogenesis of glaucomatous optic neuropathy remain unclear. Here we define early molecular events in the ONH in an inherited large animal glaucoma model in which ONH structure resembles that of humans. Gene expression profiling of ONH tissues from rigorously phenotyped feline subjects with early-stage glaucoma and precisely age-matched controls was performed by RNA-sequencing (RNA-seq) analysis and complementary bioinformatic approaches applied to identify molecular processes and pathways of interest. Immunolabeling supported RNA-seq findings while providing cell-, region-, and disease stage–specific context in the ONH in situ. Transcriptomic evidence for cell proliferation and immune/inflammatory responses is identifiable in early glaucoma, soon after IOP elevation and prior to morphologically detectable axon loss, in this large animal model. In particular, proliferation of microglia and oligodendrocyte precursor cells is a prominent feature of early-stage, but not chronic, glaucoma. ONH microgliosis is a consistent hallmark in both early and chronic stages of glaucoma. Molecular pathways and cell type–specific responses strongly implicate toll-like receptor and NF-κB signaling in early glaucoma pathophysiology. The current study provides critical insights into molecular pathways, highly dependent on cell type and sub-region in the ONH even prior to irreversible axon degeneration in glaucoma.
|
| |
|
| Overall design |
Optic nerve head mRNA profiles of feline congenital glacoma cats and age-matched normal cats were generated, using illumina Hiseq 2000.
|
| Web link |
https://doi.org/10.1007/s12035-020-01910-9
|
| |
|
| Contributor(s) |
Oikawa K, Ver Hoeve JN, Teixeira LB, Snyder KC, Hennes-Beean EA, Rasmussen CA, Kiland JA, Ellinwood NM, McLellan GJ |
| Citation(s) |
32266645 |
| |
| Submission date |
Feb 01, 2018 |
| Last update date |
Apr 09, 2020 |
| Contact name |
Kazuya Oikawa |
| Organization name |
University of Wisconsin-Madison
|
| Street address |
1300 University Ave
|
| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53705 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17081 |
Illumina HiSeq 2000 (Felis catus) |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA432566 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE110019_FPKM.txt.gz |
689.8 Kb |
(ftp)(http) |
TXT |
| GSE110019_Felis_catus_8.0.gtf.gz |
5.0 Mb |
(ftp)(http) |
GTF |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...